Hyperthermic Intraperitoneal Chemotherapy Group Research Articles

The safety and effectiveness of prophylactic hyperthermic intraperitoneal chemotherapy in patients with pathological T3-4 locally advanced colon cancer

The safety and effectiveness of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in pathological T3-4 locally advanced (pT3N+M0 and pT4NxM0) colon cancer (CC) patients with radical resection need further study. Clinical and pathological information of pT3-4 locally advanced CC patients who received radical surgery in our hospital from January 2018 to December 2020 were analyzed. The prognosis of patients was estimated using Cox proportional hazards regression analysis and Kaplan-Meier method. Among 927 patients, 10.4% (96/927) received prophylactic HIPEC based on 5-FU, 4.6% (43/927) received prophylactic HIPEC based on lobaplatin, 85.0% (788/927) received conventional therapy. The incidence of metachronous peritoneal carcinomatosis (mPC) was 9.4%. Complications occurred in 32 patients (4.1%) in the conventional therapy group, 6 patients (6.3%) in the prophylactic HIPEC group based on 5-FU and 3 patients (7.0%) in the prophylactic HIPEC group based on lobaplatin within 30 days after surgery (5-FU vs. conventional therapy group, p=0.464; Lobaplatin vs. conventional therapy group, p=0.591). Multivariate Cox regression analysis revealed that prophylactic HIPEC based on either 5-FU or lobaplatin regimen could not effectively improve mPC-free survival (5-FU: p=0.020, HR=1.927, 95% CI, 1.111-3.343; Lobaplatin: p=0.167, HR=0.247, 95% CI, 0.034-1.796), overall survival (5-FU: p=0.361, HR=1.360, 95% CI, 0.703-2.634; Lobaplatin: p=0.780, HR=0.816, 95% CI, 0.195-3.416) and disease-free survival (5-FU: p=0.525, HR=1.149, 95% CI, 0.749-1.760; Lobaplatin: p=0.117, HR=0.488, 95% CI, 0.199-1.198). Early prophylactic HIPEC based on 5-FU or lobaplatin subsequent to radical resection for patients with pT3-4 locally advanced CC is safe, but not effective in reducing the risk for mPC.

Abstract 2825: Experimental hyperthermic intraperitoneal chemotherapy in mice: Establishment of a novel ovarian cancer xenograft model

Abstract Introduction: The peritoneum is a common metastatic site for several abdominal cancers, including ovarian and colorectal cancer. Peritoneal metastasis is associated with poor prognosis and poor response to therapy. A potentially curative treatment is cytoreductive surgery (CRS) to remove all visible tumor tissue, followed by perfusion with hyperthermic intraperitoneal chemotherapy (HIPEC) to eliminate small residual tumors and free-floating tumor cells. Hyperthermia can enhance the cytotoxic effect of the drug, inhibit DNA repair and activate the immune system. At the current time, there is no standardized protocol for performing HIPEC, and there is a large variation regarding key parameters, such as choice of drug, drug concentration, treatment duration, carrier solution, volume and temperature. The impact of these parameters is unknown, and in vivo models can be a helpful tool to better understand some of these parameters to improve this treatment strategy. Methods: HIPEC was established in a murine xenograft model of ovarian cancer to evaluate the response to intraperitoneal perfusion of cisplatin and mitomycin C for 30 min at 41.5°C (HIPEC) and 37°C (NIPEC) compared to no treatment or intraperitoneal perfusion with saline at 41.5°C. The luciferase transfected B76 ovarian cancer cell line was injected intraperitoneally and treatment was performed on day 4 when the tumors were < 2 mm. Treatment efficacy was assessed by weekly luminescence measurement, tumor weight at an early time point (day 17), and overall survival. Results: Intraperitoneal perfusion with cisplatin or mitomycin C significantly inhibited tumor growth as assessed by luminescence, tumor weight on day 17, as well as increased overall survival of the mice compared to control treatment from 25-27 days to 36 days for cisplatin and 37 days for mitomycin C. No significant differences in tumor growth or survival were observed by the addition of hyperthermia. However, a slight reduction of tumor weight at day 17 was observed in the HIPEC groups. Conclusion: We have established a functional closed HIPEC model in mice bearing peritoneal metastases from the B76 ovarian cancer cell line which accurately mimics many features of the procedure in patients. Intraperitoneal perfusion of both cisplatin and mitomycin C efficaciously inhibited tumor growth and improved overall survival of the mice. Addition of hyperthermia caused an additional modest, temporary growth inhibition which did not translate into improved long-term outcome. Citation Format: Karianne Giller Fleten, Yvonne Andersson, Emil Løvstakken, Theodor M. Herud, Stein Waagene, Kjersti Flatmark. Experimental hyperthermic intraperitoneal chemotherapy in mice: Establishment of a novel ovarian cancer xenograft model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2825.

Complexity of surgery and treatment burden in patients with peritoneal malignancy is not determined by addition of hyperthermic intraperitoneal chemotherapy.

This study describes surgical and quality of life outcomes in patients with peritoneal malignancy treated by cytoreductive surgery (CRS) alone compared with a subgroup treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC). Peritoneal malignancy patients undergoing surgery between 2017 and 2023 were included. The cohort was divided into patients treated by CRS and HIPEC and those treated by CRS without HIPEC (including CRS only or maximal tumour debulking (MTB)). Main outcomes included surgical outcomes, survival, and quality of life. Groups were compared using non-parametric tests and log-rank test was used to compare survival curves. 403 had CRS and HIPEC, 25 CRS only and 15 MTB. CRS and HIPEC patients had a lower peritoneal carcinomatosis index (12.0 vs. 17.0 vs. 35.0; P < 0.001) and longer surgical operative time (9.3 vs. 8.3 vs. 5.2 h; P < 0.001), when compared to CRS only and MTB, respectively. No other significant difference between groups was observed. The optimal management of selected patients with resectable peritoneal malignancy incorporates a combined strategy of CRS and HIPEC. When HIPEC is not utilized, due to significant residual disease or comorbidity precluding safe delivery, CRS alone is associated with good outcomes. Hospital stay and complications are acceptable but not significantly different to the CRS and HIPEC group. CRS alone is a complex intervention requiring comparable resources with good outcomes. In view of our findings 'intention to treat' with CRS and HIPEC should be the basis for resource allocation and funding.

Oncological outcomes and hospitalization cost of hyperthermic intraperitoneal chemotherapy (HIPEC) open and closed abdomen techniques: Results from two French expert centers

BackgroundHyperthermic intraperitoneal chemotherapy (HIPEC) associated with CC0 excision is performed using either an open (OPEN_HIPEC) or closed abdominal technique (CLOSED_HIPEC). However, little data is available on the costs of this treatment, as there is no code for HIPEC in the French Classification of Medical Acts. Oncological outcomes and the mean cost of hospitalization were compared. MethodsBetween 2017-2021, 144 patients with peritoneal carcinomatosis (all etiologies) were included (OPEN_HIPEC, n = 70; CLOSED_HIPEC, n = 74) in this retrospective two-center study. Morbi-mortality, overall survival (OS), recurrence-free-survival (RFS) and mean cost of hospitalization were compared. ResultsThe median OS and RFS were 71.3 months [63–71.5] and 26.8 months [20–35.3] respectively, and were similar for both techniques; and after stratification by histology. Multivariate analysis adjusted on PCI score of OS identified mitomycin as a protective factor (HR = 0.31 [0.10–0.90], p = 0.032) and ASA score>2 as a risk factor of RFS (HR = 2.21 [1.28–3.83], p = 0.004). Complication rates at day 30 were similar between OPEN and CLOSED_HIPEC, 31 (44.3 %) vs 42 (56.8 %); p = 0.135. OPEN_HIPEC had more severe complications (11(35.5 %) vs 6(14.3 %); p = 0.034). The mean cost of hospitalization was estimated as €15,627 for OPEN_HIPEC and €14,211 for CLOSED_HIPEC for a mean length-of-stay of 12.7 and 16.7 days respectively. The mean amount received by the hospital per hospitalization was estimated at €16,399 and €15,536 respectively. ConclusionsOS and RFS were similar for open and closed HIPEC. Severe complications at day 30 were more frequent in OPEN_HIPEC group. The amount received by hospital for both HIPEC techniques is sufficient.

Prophylactic hyperthermic intraperitoneal chemotherapy in T4 colorectal cancer: Can it improve the oncologic prognosis? – A propensity score matching study

BackgroundSome studies show that cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) may improve overall survival and is a possible curative treatment for selected colorectal cancer (CRC) patients with restricted peritoneal metastasis (PM). The value of HIPEC in preventing PM of CRC is still controversial. Materials and methodsIn this retrospective propensity score matching (PSM) cohort study, all patients with cT4N0-2M0 undergoing treatment at a single institution in China (2014–2018) were reviewed. The 3-year disease-free survival (DFS) was set as the primary outcome, and the 3-year PM rate was also analyzed. Results220 patients were included in this study for analysis. After 1:3 PSM: HIPEC (n = 45) and No HIPEC (n = 135). Through analysis, it was found that prophylactic HIPEC correlated to better DFS [hazard ratio (HR) 0.43, 95 % confidence interval (CI) 0.19–0.95; p = 0.037], and N2 stage correlated to worse DFS [HR 1.97, 95 % CI 1.09–3.56; p = 0.025]. For laparoscopic surgery subgroup analyses, 3-year PM rate of patients with laparoscopic surgery was 13.8 % in No HIPEC group, and 2.6 % in HIPEC group (p = 0.070). Besides, no post-operative death occurred, the anastomotic leakage rate was 2.2 % in HIPEC group and 0.7 % in the control group (p = 0.439). ConclusionsProphylactic HIPEC may improve the prognosis in patients with cT4N0-1M0 CRC, but not in cT4N2M0 CRC, and it does not significantly increase surgery-related complications. Laparoscopic surgery followed by HIPEC for T4 stage CRC may not increase risk of PM.

Effect of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy on epithelial ovarian, fallopian tube, and peritoneal cancer: An institutional review of outcomes and its clinical implications

BACKGROUND: Ovarian, fallopian tube, and peritoneal cancer patients with advanced-stage diagnosis or recurrences spread to the peritoneal surface of the abdomen. Hyperthermic intraperitoneal chemotherapy (HIPEC) can penetrate and eradicate tumors that are microscopic up to those with a diameter of 2.5 cm from the peritoneal surface following cytoreductive surgery (CRS). OBJECTIVES: The study aimed to determine the efficacy and safety of CRS with HIPEC versus CRS alone for patients with epithelial ovarian, fallopian tube, and peritoneal cancer. MATERIALS AND METHODS: This retrospective cohort study included 50 patients (20 patients underwent CRS + HIPEC, while 30 patients underwent CRS alone). Records of these patients from January 2014 to June 2020 were reviewed, tabulated, and analyzed. RESULTS: The difference in recurrence rate between CRS with HIPEC and CRS alone was not statistically significant (50% vs. 43%, P = 0.774). The median time to recurrence was 10 and 9 months, respectively (P = 0.636). Five percent in the HIPEC group succumbed to the disease, while 13% died in the CRS alone group (P = 0.636). More post-operative complications were noted in the HIPEC group (45% vs. 10%, P = 0.007), but among these, only 2 cases had grade 3 to 4 complications (10%). The addition of HIPEC in the management of these patients resulted in a longer operative time (360 vs. 240 min, P &lt; 0.001) and postoperative hospital stay (8 vs. 6 days, P = 0.026). There were no intra- or peri-operative mortalities in both groups. CONCLUSION: CRS with HIPEC and CRS alone showed similar time to recurrence and recurrence rate. CRS with HIPEC had low risk of grade 3-4 complications and may still be considered as a treatment option for advanced, progressive, and recurrent epithelial ovarian, fallopian tube, and peritoneal cancer.

Hyperthermic Intraperitoneal Chemotherapy (HIPEC): New Approaches and Controversies on the Treatment of Advanced Epithelial Ovarian Cancer-Systematic Review and Meta-Analysis.

Hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery has been extensively studied in patients with peritoneal carcinomatosis, and it holds promise as a therapeutic strategy, but its role remains elusive. The aim of this study was to assess the existing evidence for the use or not of HIPEC in primary debulking surgery (PDS), interval debulking surgery (IDS), and recurrent ovarian cancer (ROC), evaluated in terms of survival rates and post-surgical morbidity. Medline, Pubmed, Cochrane, and Medscape were systematically searched for any article comparing the use of HIPEC treatment with any other therapy in patients with ovarian cancer in PDS, IDS, and ROC. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines were followed. We only considered English-language published studies. We included 14 studies, including two RCTs with a total of 1813 women, published between 2003 and 2023 with a recruitment period between 1998 and 2020. In PDS, there were no differences in progression-free survival (PFS) between HIPEC and controls [MD -5.53 months [95% CI -19.91 to 8.84 months]; I2 = 96%]. Conversely, in patients treated with NACT, pooled results showed a significant survival advantage in terms of progression-free survival (PFS) and overall survival (OS) in the combined HIPEC plus IDS group rather than surgery alone [PFS: MD 4.68 months (95% CI 3.49 to 5.86 months, I2 = 95%); OS: MD 11.81 months (95% CI 9.34 to 14.27 months); I2 = 97%]. Concerning ROC patients, pooled MD did not show either a significant PFS difference between intervention and controls [MD 2.68 months (95% CI 433 to 9.70 months); I2 = 95%], and OS significant difference (MD 6.69 months [95% CI -9.09 to 22.47 months]; I2 = 98%). Severe post-operative complications (≥grade 3) were available in 10 studies, accounting for 1108 women. Overall, there was a slightly but significantly increased risk with the combined approach compared to controls [RR 1.26 (95% CI 1.02 to 1.55); I2 = 0%]. The combination of HIPEC with cytoreductive surgery prolongs OS and PFS in advanced epithelial ovarian cancer after NACT with acceptable morbidity. However, additional trials are still needed to determine the effectiveness of HIPEC in primary and recurrence settings. In the era of personalized medicine, the correlation between the efficacy of HIPEC and biological and molecular findings represents a challenge for the future of ovarian cancer.

Outcomes Following Cytoreductive Surgery and Hyperthermic Intraoperative Thoraco-Abdominal Chemotherapy with Diaphragm Resection for Peritoneal Carcinomatosis: A Retrospective Cohort Study.

We aimed to evaluate the safety and efficacy of hyperthermic intraoperative thoraco-abdominal chemotherapy (HITAC) and cytoreductive surgery (CRS) for peritoneal carcinomatosis (PC) patients who underwent diaphragm resection. PC patients who underwent CRS with diaphragm resection were selected from a prospectively established database and were divided into hyperthermic intraperitoneal chemotherapy (HIPEC) and HITAC groups. The clinicopathological characteristics, treatment-related variables, perioperative adverse events (AEs), and survival outcomes were compared between the two groups. Of 1168 CRS + HIPEC/HITACs, 102 patients were enrolled-61 HITAC patients and 41 HIPEC patients. In the HITAC and HIPEC groups, the incidence of grade III-V AEs was 29.5% versus 34.1% (p = 0.621). The pleural progression rates were 13.2 versus 18.9% (p = 0.462) and the median overall survival (OS) was 50.5 versus 52.7 months (p = 0.958). Median time to progression (TTP) in thoracic disease was not reached. There was no significant difference in perioperative AEs, TTP, and OS for total patients and the completeness of cytoreduction (CC) score subgroups (p > 0.05). Age ≥ 60years (hazard ratio [HR] 4.162, p = 0.026) was an independent risk factor influencing pleural progression, and primary malignant peritoneal mesothelioma (MPM; HR 2.749, p = 0.016) and the presence of two or more serious AEs (SAEs; HR 7.294, p = 0.001) were independent risk factors influencing OS. HITAC can be performed in carefully selected PC patients who underwent diaphragm resection, with no worsening of the safety profile and a possible benefit for pleural progression. In those patients, age ≥ 60 years is associated with a shorter TTP of thoracic disease, while primary MPM and two or more perioperative SAEs are associated with worse OS.

The safety and efficacy of prophylactic hyperthermic intraperitoneal chemotherapy for elderly patients with locally advanced gastric cancer: a propensity score matching analysis

Objective: To evaluate the safety and efficacy of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) on elderly patients diagnosed with locally advanced gastric cancer based on a propensity score matching analysis. Methods: Clinical data of elderly patients with locally advanced gastric cancer who underwent radical gastrectomy in Beijing Hospital from January 2017 to December 2021 were retrospectively collected. According to whether HIPEC was used, the patients were divided into HIPEC group (radical gastrectomy combined with HIPEC) and control group (radical gastrectomy alone), and 29 patients in HIPEC group and 122 patients in control group. After 1∶1 matching of PSM, there were 28 patients in each group. The clinicopathological data, surgical data, postoperative recovery and long-term survival of the two groups were compared and analyzed. Results: Before PSM, the mean age in the HIPEC group was (70.7±4.0) years, and in the control group was (73.1±5.8) years (P=0.011). After PSM, the mean age in the HIPEC group was (70.9±3.9) years, and it was (71.8±5.4) years in the control group (P=0.739). Before PSM, the incidence of postoperative complications was 20.7% (6 cases) in the HIPEC group and 26.2% (32 cases) in the control group (P=0.639). After PSM, the incidence of postoperative complications was 21.4% (6 cases) in the HIPEC group and 14.3% (4 cases) in the control group (P=0.730). Before PSM, the mean duration of hospitalization after radical gastrectomy was (13.6±7.6) days in HIPEC group and (16.2±13.0) days in control group, respectively (P=0.312). After PSM, the mean duration of hospitalization after radical gastrectomy was (13.7±7.8) days in HIPEC group and (15.4±9.7) days in control group, respectively (P=0.479). Before PSM, the 1-and 3-year overall survival rates of the HIPEC group were 88.2% and 69.7%, and 88.0% and 66.1% for control group, respectively, with no statistical difference between the two groups in overall survival (P=0.499). After PSM, the 1-and 3-year overall survival rates of the HIPEC group were 86.8% and 69.7%, and 93.1% and 67.5% for control group, respectively, with no statistical difference between the two groups in overall survival (P=0.425). Before PSM, the 1-and 3-year disease-free survival rates of the HIPEC group were 88.2% and 67.1%, and 87.8% and 64.3% for control group, respectively, with no statistical difference between the two groups in disease-free survival (P=0.863). After PSM, the 1-and 3-year disease-free survival rates of the HIPEC group were 88.2% and 62.8%, and 93.7% and 64.7% for control group, respectively, with no statistical difference between the two groups in disease-free survival (P=0.804). Conclusions: Radical surgery combined with HIPEC for elderly patients with gastric cancer does not increase postoperative complications and postoperative recovery time. However, there was no significant difference in overall survival and disease-specific survival between the two groups.

Prognostic Analysis of Prophylactic Hyperthermic Intraperitoneal Chemotherapy for Advanced Gastric Cancer: a Propensity Score-Matched Analysis

PurposeTo investigate the efficacy of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer (AGC). MethodsWe included 198 patients treated from December 2016 to January 2019; of these patients, the 132 who had clinical T4 gastric cancer were divided into a hyperthermic intraperitoneal chemotherapy group (HIPEC group) and a radical gastrectomy and D2 lymph node dissection group (control group). Because this study was retrospective, we used propensity score matching (PSM) to reduce selectivity bias; we then assessed risk factors for recurrence and compared prognosis in terms of survival in the gastrectomy and prophylactic HIPEC groups. ResultsProphylactic HIPEC reduced the risk of postoperative peritoneal metastasis (PM: 27.5% vs. 10.5%, P = 0.015) and did not increase the risk of postoperative complications, but there was no significant difference in the effect on hepatic metastases or other distant metastases. Risk factors for recurrence included pT4 staging and positive lymph node metastases. Both disease-free survival (DFS: HR 0.592; 95% CI 0.354–0.990; P = 0.042) and peritoneal recurrence-free survival (PFS: HR 0.314; 95% CI 0.127–0.774; P = 0.008) were better in the prophylactic HIPEC group than in the gastrectomy-only group. In addition, there was no difference in the prognosis of patients between the two groups of raltitrexed (RT) and paclitaxel (PTX) for perfusion dosing. ConclusionOur study showed that prophylactic HIPEC could prevent postoperative PM in patients with AGC and did not increase the incidence of postoperative complications. However, it was not found to be effective in the prevention of other metastases, such as hepatic metastases.

Hyperthermic Intraperitoneal Chemotherapy After Interval Cytoreductive Surgery for Patients With Advanced-Stage Ovarian Cancer Who Had Received Neoadjuvant Chemotherapy

Hyperthermic intraperitoneal chemotherapy (HIPEC) followed by interval cytoreductive surgery (ICS) has shown survival benefits for patients with advanced-stage ovarian cancer. However, there is still a lack of consensus regarding the integration of HIPEC into clinical practice. To evaluate the safety and effectiveness of ICS with HIPEC compared with ICS alone in clinical practice for patients with advanced-stage ovarian cancer. This prospective, multicenter, comparative effectiveness cohort study enrolled 205 patients with stage III or IV ovarian cancer who had received at least 3 cycles of neoadjuvant chemotherapy followed by ICS with HIPEC or ICS without HIPEC at 7 Korean Gynecologic Oncology Group institutions between September 1, 2017, and April 22, 2022. Nine patients were excluded because they did not meet the inclusion criteria. Neoadjuvant chemotherapy followed by ICS with HIPEC or ICS without HIPEC. The primary end point was progression-free survival (PFS). Overall survival (OS) and the safety profile were the key secondary end points. This study included 196 patients (median age, 58.0 years [range, 38-82 years]), of whom 109 underwent ICS with HIPEC and 87 underwent ICS without HIPEC. The median duration of follow-up was 28.2 months (range, 3.5-58.6 months). Disease recurrence occurred in 128 patients (65.3%), and 30 patients (15.3%) died. Interval cytoreductive surgery with HIPEC was associated with a significant improvement in median PFS compared with ICS without HIPEC (22.9 months [95% CI, 3.5-58.6 months] vs 14.2 months [95% CI, 4.0-56.2 months]; P = .005) and median OS (not reached [95% CI, 3.5 months to not reached] vs 53.0 [95% CI, 4.6-56.2 months]; P = .002). The frequency of grade 3 or 4 postoperative complications was similar in both groups (ICS with HIPEC, 3 of 109 [2.8%] vs ICS without HIPEC, 3 of 87 [3.4%]; P > .99). Among patients with recurrence, the frequency of peritoneal recurrence was lower in the ICS with HIPEC group than in the ICS without HIPEC group (21 of 64 [32.8%] vs 41 of 64 [64.1%]; P = .001). This study suggests that ICS in conjunction with HIPEC was associated with longer PFS and OS than ICS without HIPEC for patients with advanced-stage ovarian cancer and was not associated with higher rates of postoperative complications. The lower rate of peritoneal recurrence after HIPEC may be associated with improved OS.

HIPEC in Ovarian Cancer: When and to Whom?

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.

Effect of hyperthermic intraperitoneal chemotherapy on survival and recurrence rates in advanced gastric cancer: a systematic review and meta-analysis.

Around 5-20% of patients who undergo surgery for advanced gastric cancer (AGC), which invades into the muscularis propria or beyond, have peritoneal carcinomatosis. The peritoneal recurrence rate is 10-54%, which is associated with a poor prognosis. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) in AGC with and without peritoneal carcinomatosis is not clearly defined. The authors conducted a meta-analysis, in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, of the clinical trials and high-quality nonrandomized studies evaluating the role of HIPEC in AGC over the last 10 years. The studies were searched in PubMed, EMBASE, MEDLINE, and Cochrane databases between January 2011 to December 2021. Clinical data including overall survival, recurrence free survival, overall recurrence rate, peritoneal recurrence rate, and complications analyzed using RevMan 5.4. Six randomized controlled trials and 10 nonrandomized studies, comprising a total of 1700 patients were included. HIPEC was associated with significantly improved OS at 3 [odd ratio (OR) 1.89, 95% CI: 1.17-3.05] and 5 years (OR 1.87, 95% CI: 1.29-2.71). HIPEC was associated with reduced overall recurrence (OR 0.49, 95% CI: 0.31-0.80) and peritoneal recurrence (OR 0.22, 95% CI: 0.11-0.47). HIPEC was not associated with increased complications. The occurrence of postoperative renal dysfunction was significantly higher in the HIPEC group (OR 3.94, 95% CI: 1.85-8.38). The role of HIPEC in AGC has evolved over the past decade. HIPEC may improve survival rates and reduce recurrence rates in patients with AGC, without significant increase in complications and with a favorable impact on 3 and 5-year survival.

#4934 HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY WITH CISPLATIN INCREASES THE RISK OF ACUTE KIDNEY INJURY COMPARED TO CONVENTIONAL INTRAPERITONEAL CISPLATIN

Abstract Background and Aims Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin is increasingly used for the treatment of ovarian and peritoneal cancer. Acute kidney injury (AKI) is a frequent complication after cisplatin containing HIPEC therapy. The aim of this study was to compare the incidence and severity of AKI and renal survival after HIPEC compared to repeated cycles of conventional high-dose intraperitoneal cisplatin in patients with ovarian and malignant peritoneal cancer. Method We conducted a retrospective study that included patients with ovarian cancer that received repeated cycles of high-dose intraperitoneal cisplatin and patients with ovarian and primary malignant peritoneal cancer that received HIPEC with cisplatin in our center between August 2006 and September 2022. Demographic and perioperative data were compared between both groups. We compared the incidence of AKI defined as a rise in serum creatinine by ≥ 0.3 mg/dL within 48 hours (KDIGO criteria), the severity of AKI defined as stages I, II and III using the KDIGO staging, the rate of kidney function recovery and need for renal replacement therapy in both groups. We performed logistic regression analysis to identify independent risk factors for experiencing AKI and conducted survival analyses and multivariate Cox regression analyses to detect independent risk factors for patient survival. Results The study included 39 patients; 20 received 76 cycles of conventional intraperitoneal cisplatin, and 19 patients (13 with ovarian cancer and 6 with primary peritoneal cancer) received HIPEC. Patients who received HIPEC were older (63.4±20 years vs 56±8 years, p = 0.002) and received a lower dose of cisplatin both in absolute values (109.2±41.1 mg vs 159.2±15.2 mg, p&amp;lt;0.001) and adjusted by body surface area (63.4±19.9 mg/m2 vs 96.8±9.2 mg/m2, p&amp;lt;0.001). AKI was significantly more frequent in patients receiving HIPEC (42.1% vs 15.8%, p = 0.012), and was more severe after HIPEC with AKIN-I, AKIN-II and AKIN-III in 50% vs 83%, 12.5% vs 16.7% and 37.5% vs 0% respectively, p = 0.042. Recovery from AKI was more frequent in patients receiving conventional intraperitoneal cisplatin (100% vs 50%, p = 0.014) and 1 patient in the HIPEC group progressed to end stage kidney disease. In the multivariate logistic regression analysis, after adjusting for age, baseline serum creatinine and cisplatin dose, treatment with HIPEC compared to conventional high-dose intraperitoneal cisplatin remained a significant risk factor for developing AKI (OR 1550, CI 95% 19-128070). Conclusion Cisplatin-based HIPEC therapy is associated with an increased risk of severe AKI compared to conventional high-dose intraperitoneal cisplatin regimens, despite the use of prophylactic measures. Hyperthermic perfusion of the abdomen might be an important contributing factor in HIPEC-induced renal injury. To reduce the incidence of AKI and its associated morbidity after HIPEC, early implementation of preventive measures with adequate fluid management and closer monitoring of hemodynamic parameters and kidney function tests should be taken into consideration.

Prophylactic hyperthermic intraperitoneal chemotherapy in T4 colorectal cancer: Can it improve the oncologic prognosis?

3619 Background: Previous studies have shown that T4 stage was one of the risk factors for peritoneal metastasis (PM) of colorectal cancer (CRC). However, there is paradoxical data to prove that prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) treatment is beneficial for CRC patients. Methods: In this cohort study, 220 consecutive CRC patients with T4N0-2M0 were enrolled and recorded from November 2014 to November 2018 with a 3-year follow-up following surgery. A propensity score matching (PSM) approach was applied to balance the clinicopathological characteristics. Finally, 180 patients were matched successfully to further analyze. The 3-year disease-free survival (DFS) was set as the primary outcome, and the PM rate between the two groups after PSM was analyzed. Results: Before PSM, of 220 CRC patients enrolled, the 3-year DFS was 83.9% in the HIPEC group, which was better than 67.2% in the control group. The cumulative PM incidence was 2.2% in the HIPEC group and 12.6% in the control group (p = 0.047). After PSM, 180 matched patients were formed for further analysis. The DFS and the cumulative PM rate of the patients in the HIPEC group were also better than that in the control group (p = 0.034 and 0.047, respectively). For laparoscopic surgery subgroup analyses, PM rate of the patients with laparoscopic surgery was 13.8% in the No HIPEC group, and 2.6% in the HIPEC group (p = 0.070). Through multivariable analysis, it was found that prophylactic HIPEC correlated to better DFS [hazard ratio (HR) 0.43, 95% confidence interval (CI) 0.19-0.95; p = 0.037], and N2 stage correlated to worse DFS [HR 1.97, 95% CI 1.09-3.56; p = 0.025]. Besides, no post-operative death occurred, the anastomotic leakage rate was 2.2% in the HIPEC group and 0.7% in the control group (p = 0.439). Conclusions: Prophylactic HIPEC may improve the prognosis in the patients with T4N0-1M0 CRC, but not in the T4N2M0 CRC, and it does not significantly increase the surgery-related complications. Laparoscopic surgery followed by HIPEC for T4 stage CRC is relatively safe, which does not increase the risk of PM.

Survival and complications of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in patients with intra-abdominal malignancies: A meta-analysis of randomized controlled trials.

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.

Lobaplatin-based prophylactic hyperthermic intraperitoneal chemotherapy for T4 gastric cancer patients: A retrospective clinical study.

To explore the clinical efficacy of lobaplatin-based prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with T4 gastric cancer after surgery and to evaluate its impact on survival. Data on patients with T4 gastric cancer who underwent radical gastric resection between March 2016 and August 2017 were collected from the National Cancer Center and Huangxing Cancer Hospital. Enrolled patients were divided into two groups according to receiving or not receiving HIPEC. A total of 106 patients were included in this study; among them, 51 patients underwent radical gastric resection plus prophylactic HIPEC, and 55 patients underwent radical gastric resection only. The baseline characteristics were well balanced between the two groups. The postoperative platelet counts in the HIPEC group were significantly lower than those in the non-HIPEC group (P< 0.05); however, we did not observe any occurrences of serious bleeding in the HIPEC group. There were no significant differences in the postoperative complication rates between the two groups (P > 0.05). The postoperative (1 month) CEA, CA19-9, and CA72-4 levels in the HIPEC group were significantly decreased in the HIPEC group (P < 0.05). At a median follow-up of 59.3 months, 3 (5.5%) patients in the HIPEC group experienced peritoneal recurrence, and 10 (18.2%) patients in the non-HIPEC group experienced peritoneal recurrence (P < 0.05). Both groups had comparable 5-year overall survival (OS) rates (41.1% HIPEC group vs. 34.5% non-HIPEC group, P = 0.118). The 5-year disease-free survival was significantly higher in the HIPEC group than in the non-HIPEC group (28.6% versus 39.7%, p = 0.046). Lobaplatin-based prophylactic HIPEC is feasible and safe for patients with T4 gastric cancer and does not increase postoperative adverse effects. The use of HIPEC showed a significant decrease in the incidence of local recurrence rates and blood tumor marker levels. The 5-year disease-free survival was significantly higher in the HIPEC group; however, the 5-year OS benefit was not found in T4 stage patients.

Closed hyperthermic intraperitoneal chemotherapy with CO2 recirculation system compared with the open Coliseum technique in peritoneal malignity treatment

BackgroundCytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis can be performed in two ways: first, the standard open abdominal technique (Open HIPEC); or second, the closed technique. In recent years, a new technique has been introduced to perform closed HIPEC; the Peritoneal Recirculation System (PRS-1.0 Combat) with CO2 recirculation technology (PRS Closed HIPEC). The objective of this study is to present our experience with the PRS Closed HIPEC by comparing the intraoperative, postoperative and oncological results with the standard Open HIPEC technique (the Coliseum technique). MethodsData on patients undergoing CRS and HIPEC at the Sanchinarro University Hospital, Madrid from October 2012 to June 2021 were collected in a prospective database. The inclusion criteria were patients with primary or recurrent peritoneal metastases in gastrointestinal malignancies or ovarian cancer. The presence of an unresectable peritoneal carcinomatosis, the coexistence of another oncological disease, unresectable and distant metastases were the exclusion criteria. ResultsFrom October 2014 to June 2021, 84 patients underwent CRS and HIPEC at the Sanchinarro University Hospital, Madrid with curative intent. Since the introduction of the PRS Closed HIPEC technique in 2016, 65 patients have been treated. Before the introduction of PRS Closed HIPEC, 19 cases were performed using the Coliseum technique (the Open HIPEC group). The intraoperative results were similar in the two groups. Complete cytoreduction was achieved in all cases in the Open HIPEC group and in 98% in the PRS Closed HIPEC group. The rate of major complications was similar between the groups. Median Overall Survival (OS) resulted better in the Closed HIPEC group (67 months) with respecto to the Open group (43 months) (p < 0,001). Median Disease-Free Survival (DFS) was 15 months in the Open HIPEC group and 40 months in the PRS Closed HIPEC group (p < 0.001). ConclusionThe Peritoneal Recirculation System with CO2 recirculation technology (PRS Closed HIPEC) is a reproducible and safe technique and may represent a valid alternative for the administration of HIPEC.

Cost-effectiveness of hyperthermic intraperitoneal chemotherapy following interval cytoreductive surgery for stage III-IV ovarian cancer from a randomized controlled phase III trial in Korea (KOV-HIPEC-01)

BackgroundTo evaluate the cost-effectiveness of the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) following interval cytoreductive surgery (ICS) for stage III-IV ovarian cancer from a randomized controlled phase III trial. MethodsA comparative cost-effective analysis was performed using a Markov health-state transition model derived from the current trial cohort (ClinicalTrials.gov Identifier: NCT01091636). The incremental cost-effectiveness ratio (ICER) was evaluated by dividing the incremental costs by incremental quality-adjusted life-years (QALYs) with a time horizon of 10 years. Costs were calculated from the perspective of Korean healthcare, and health utility values were extracted from published sources. ResultsBased on data from the trial, the mean QALY in the ICS group was 7.16 compared to 10.8 in ICS followed by the HIPEC group. With an incremental QALY of 3.64, the ICS followed by HIPEC, was estimated to obtain an ICER of KRW 954,598 (USD 708.3) per QALY. ConclusionThe findings of the study suggest that ICS followed by HIPEC, is cost-effective with a significant gain in QALYs. These results may support the current reimbursement of HIPEC from Korean insurance services and the management of long-term conditions.

Ten-year treatment outcomes of consolidation hyperthermic intraperitoneal chemotherapy for ovarian cancer (HIPEC-KOV-03R).

We aimed to evaluate the long-term efficacy of consolidation hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with primary epithelial ovarian cancer. This retrospective cohort study included patients who underwent second-look surgery either with or without HIPEC after having complete or partial response to primary cytoreductive surgery and adjuvant platinum-based chemotherapy between January 1991 and December 2003 at Seoul St. Mary's Hospital. The 10-year progression-free survival (PFS), overall survival (OS), and toxicity within postoperative 28 days were investigated. A total of 87 patients were identified, 44 (50.6%) received second-look surgery with HIPEC whereas 43 (49.4%) received only second-look surgery. The 10-year PFS and OS were significantly longer in the HIPEC group compared with the control group (PFS, 53.6% vs. 34.9%, log-rank p=0.009; OS, 57.0% vs. 34.5%, log-rank p=0.025). Multivariable analysis identified HIPEC as an independent favorable prognostic factor for PFS (adjusted hazard ratio [HR]=0.42; 95% confidence interval [CI]=0.23-0.77; p=0.005) but not for OS (adjusted HR=0.58; 95% CI=0.32-1.07; p=0.079). The more common adverse events in the HIPEC group were thrombocytopenia (90.9% vs. 68.3%, p=0.005), elevated liver enzymes (65.9% vs. 29.3%, p=0.002), and wound complications (18.2% vs. 2.4%, p=0.032). However, these adverse events were reversible and did not delay subsequent consolidation chemotherapy. The consolidation HIPEC demonstrated a significant improvement in 10-year PFS but not OS, with acceptable toxicity in patients with primary epithelial ovarian cancer. Further randomized controlled trials are warranted to confirm these results.