Hyperthermic Intraperitoneal Chemotherapy Group Research Articles

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.

Hyperthermic Intraperitoneal Chemotherapy Following Cytoreductive Surgery for Colorectal Peritoneal Carcinomatosis Patients: A Review.

Colorectal peritoneal carcinomatosis (CPC) is an advanced malignancy and is typically associated with a poor prognosis. Hyperthermic intraperitoneal chemotherapy (HIPEC) following complete cytoreductive surgery (CRS) is a novel, advanced loco-regional treatment for colorectal cancer that is currently being used to treat peritoneal carcinomatosis (PC). The present review aims to describe the evidence-based literature on the efficacy and safety of this treatment approach in patients with PC originating from colorectal cancer and to summarize its complications. All published literature regarding the efficacy of HIPEC for the treatment of CPC was reviewed; 16 studies were included in this paper. The overall survival rate for the HIPEC group ranged from 63% to 93%. The overall median survival for the HIPEC and non-HIPEC groups ranged from 13 to 60.1 months and 12.6 to 41.2 months, respectively. The overall median survival of patients in the HIPEC group was comparatively better than those in the non-HIPEC group. There was insufficient evidence to suggest whether this treatment regimen was associated with a high or low morbidity rate in comparison to other groups. However, the mortality rate associated with this treatment regimen was low. In conclusion, the present data provide insufficient evidence regarding the beneficial effects of using HIPEC following CRS treatment. Therefore, further studies are required to determine the benefits of HIPEC for CPC patients.

OGC O07 Effect of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) on survival and recurrence rates in advanced gastric cancer- systematic review and meta analysis

Abstract Background Around 5–20% of patients who undergo surgery for advanced gastric cancer have peritoneal carcinomatosis and 10–54% have peritoneal recurrence after surgery, which is associated with poor prognosis. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) in advanced gastric cancer (AGC) is not clearly defined. We performed a meta-analysis to assess the safety and survival benefit of HIPEC in AGC. Methods We conducted a meta-analysis, in accordance with the PRISMA guidelines, of the clinical trials and high-quality non-randomized 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 202. The PROSPERO registration number is CRD42022310556. Clinical data including overall survival (OS), recurrence-free survival, overall recurrence rate, peritoneal recurrence rate, and complications analyzed after data extraction using RevMan5.4.The primary endpoint was overall survival. The secondary end points were 5 year survival, disease-free survival, post operative complications: myelosuppression, liver dysfunction, intestinal obstruction, leak, and mortality. The impact of HIPEC on overall and peritoneal recurrence was also evaluated. Results Six randomized controlled trials and 10 nonrandomized studies met the inclusion criteria and were included in the meta-analysis, comprising a total of 1700 patients. While the use of HIPEC did not impact OS at one year, it was associated with significantly improved OS at 3 (OR 1.89, 95% CI 1.17–3.05) and at 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% 0.11–0.47). HIPEC was not associated with increased complications; however, the occurrence of postoperative renal dysfunction was significantly higher in the HIPEC group (OR 3.94, 95% CI 1.85–8.38). 3-year mortality was significantly favorable to HIPEC (OR 0.38, 95% CI 0.18–0.82). Conclusions The role of HIPEC in AGC has evolved over the past decade. These results suggest that HIPEC may improve survival rates and reduce recurrence rates in patients with AGC, without significant increase in complications. HIPEC may improve survival rates and reduce recurrence rates in patients with AGC, without any significant increase in complications with a favorable impact on 3 and 5-year survival. The prognosis is dependent on patient selection. High quality, multi-centre trials are needed to guide in patient selection and developing standardized protocols for the management for this cohort of patients.

Hyperthermic intraperitoneal chemotherapy (HIPEC) as adjuvant and therapeutic options for patients with advanced gastric cancer at high risk of recurrence or established peritoneal metastases: a single-centre experience.

Peritoneal metastases from gastric cancer (PM-GC) have a detrimental prognostic impact on survival and there is a lack of consensus regarding treatment. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may offer a chance for prolonged survival as compared to standard chemotherapy. This study aims to present our experience in the management of GC with CRS and HIPEC. This is a single-centre retrospective study. Patients were divided into two groups: patients with GC at high risk for developing PM-GC (adjuvant HIPEC group) and patients with PM-GC or positive peritoneal cytology (therapeutic CRS and HIPEC group). Overall survival (OS) and disease-free survival (DFS) were considered as outcome measures. A total of 41 patients with a GC primary received surgery and HIPEC: 14 patients (34.1%) were in the adjuvant HIPEC group, while 27 patients (65.9%) were in the therapeutic CRS and HIPEC group. In the adjuvant HIPEC group, the 1- and 3-year OS were 85.7% and 71.4%, while 1- and 3-year DFS were 71.4% and 64.3%, respectively. In the therapeutic CRS and HIPEC group, OS was 60.3% and 35.1% at 1 and 3 years, whereas 1- and 3-year DFS were 38% and 32.6%, respectively. Univariate survival analysis of patients in the therapeutic CRS and HIPEC group showed that the presence of lymph node metastasis and signet ring cell histology predicted worse OS, while PCI > 12 and lymph node metastasis were associated with decreased DFS. Treatment of highly selected patients with GC at high risk of peritoneal recurrence or established PM with CRS and HIPEC showed satisfactory results in terms of OS and DFS.

Hyperthermic intraperitoneal chemotherapy for epithelial ovarian cancer: A meta-analysis

BackgroundThe value of hyperthermic intraperitoneal chemotherapy (HIPEC) at the time of cytoreductive surgery (CRS) for epithelial ovarian cancer (EOC) is controversial and its use remains experimental in most national and international guidelines. We wished to systematically evaluate all available evidence. MethodsA comprehensive review of data from MEDLINE, EMBASE, and Cochrane Library databases was conducted from the first report on HIPEC in EOC till April 3, 2022. Progression-free survival (PFS) and overall survival (OS) were compared between the HIPEC and control groups. This meta-analysis was registered with PROSPERO (CRD42021265810). ResultsFifteen studies (10 case-control studies and 5 randomized controlled trials [RCTs]) were included in the present meta-analysis. Based on the time interval between the last systemic chemotherapy exposure and timing of CRS +/− HIPEC, all studies and patients' cohorts we classified into recent (<6 months; n = 9 studies/patients cohorts) and non-recent (≥6 months, n = 8 studies/patients cohorts) chemotherapy exposure groups. In the recent chemotherapy exposure group, HIPEC was associated with improvement of both PFS (HR, 0.585; 95% CI, 0.422–0.811) and OS (HR, 0.519; 95% CI, 0.346–0.777). On the contrary, in the non-recent chemotherapy exposure group, HIPEC failed to significantly affect PFS (HR, 1.037; 95% CI, 0.684–1.571) or OS (HR, 0.932; 95% CI, 0.607–1.430). Consistent results were observed in subsequent sensitivity analyses. ConclusionOur present meta-analysis demonstrates that the value of HIPEC at CRS for EOC appears to depend on the timing of the last systemic chemotherapy exposure. Future trials are awaited to define the role of HIPEC in EOC.

Hyperthermic intraperitoneal chemotherapy following up-front cytoreductive surgery versus cytoreductive surgery alone for isolated synchronous colorectal peritoneal metastases: A retrospective, observational study.

To date, the value of hyperthermic intraperitoneal chemotherapy (HIPEC) following up-front resection for isolated synchronous colorectal peritoneal metastases seems controversial. This retrospective cohort study was conducted from September 1, 2012, to September 1, 2019, at a tertiary medical center in China. Patients with isolated synchronous colorectal peritoneal metastases were included in CRS plus HIPEC group or CRS alone group based on the treatment history. Overall survival and relapse-free survival were estimated using Cox proportional hazards regression analysis and Kaplan-Meier method. 78 patients with isolated synchronous colorectal peritoneal metastases were identified among 396 patients with synchronous colorectal peritoneal metastases. 43 were in the cytoreductive surgery plus HIPEC group and 35 were in the cytoreductive surgery alone group. Among them, 61 patients had relapse-free survival data. The median peritoneal cancer index was 4 in all patients. After a median follow-up of 46.0 months, 5-year overall survival was 66.8% and the median relapse-free survival was 36.0 (95% CI, 6.8-65.1) months in the CRS plus HIPEC group. 5-year overall survival was 31.2% and the median relapse-free survival was 12.0 (95% CI, 9.0-15.0) months in the CRS alone group. Cox regression analyses showed that HIPEC was the independent prognostic factor for overall survival (P = 0.004) and relapse-free survival (P = 0.049). Findings of the present study suggest that HIPEC following up-front CRS could improve overall survival and relapse-free survival in patients with isolated synchronous colorectal peritoneal metastases.

The short- and long-term survival of hyperthermic intraperitoneal chemotherapy (HIPEC) in the advanced gastric cancer with/without peritoneal carcinomatosis: a systematic review and meta-analysis of randomized controlled trials.

To evaluate the short- and long-term survival of hyperthermic intraperitoneal chemotherapy (HIPEC) in the patients with advanced gastric cancer (AGC) through randomized controlled trials (RCTs). We analyzed the endpoints of AGC patients including 1-, 2-, 3-, and 5-year overall survival (OS), intestinal anastomotic leakage, myelosuppression, nausea and vomiting from included studies. And we retrieved RCTs from medical literature databases. Risk ratios (RR) was used to calculated the endpoints. Totally, we retrieved 13 articles (14 trial comparisons) which contained 1091 patients. They were randomized to HIPEC group and control group. The results showed that there was no significant differences in survival rates between HIPEC group and control group at 1-, 2- and 3-year follow-up, while a statistical significant overall survival effect was found at the 5-year follow-up [RR: 1.20, 95% CI 1.01 to 1.43, I2 = 0.0%]. And there is no significant difference in the risk of intestinal anastomotic leakage, myelosuppression and nausea and vomiting. Compared with the control group, HIPEC could improve the long-term OS without increasing the risk of adverse effect in AGC patients with/without peritoneal carcinomatosis, but there was no benefit at short-term OS.

No obvious advantage of hyperthermic intraperitoneal chemotherapy after interval debulking surgery in the treatment of advanced ovarian cancer: A retrospective study.

ObjectiveTo study the efficacy of interval debulking surgery (IDS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) compared to IDS alone for the treatment of ovarian cancer after neoadjuvant chemotherapy (NACT).MethodsWe conducted a retrospective study of patients with stage IIIC/IV high-grade serous ovarian carcinoma who underwent surgery at our center from January 2018 to December 2019. Patients who underwent IDS after NACT with (N = 20) or without (N = 42) HIPEC were included. HIPEC was administered after surgery and was combined with 1–2 courses of intraperitoneal hyperthermic perfusion with normal saline only. We analyzed clinical information and outcomes for the two groups.ResultsThe median progression-free survival (PFS) was 14.05 months in the IDS plus HIPEC group and 12.97 months in the IDS group (P = 0.597). The median overall survival (OS) was not reached. After adjustment for age between the two groups, the differences in PFS and OS remained nonsignificant. The change ratio of postoperative CA-125 to preoperative CA-125 was 0.66 in the IDS plus HIPEC group and 0.53 in the IDS group (P = 0.341). The difference in human epididymis protein 4 (HE-4) change ratio between the two groups was nonsignificant (P = 0.225). No significant difference was observed in the occurrence of grade 3 and 4 adverse events between the two groups (P = 0.201).ConclusionAfter NACT, IDS plus HIPEC did not show significant PFS and tumor index change ratio benefits over IDS alone in patients with primary ovarian cancer. Further investigations are needed to assess the role of HIPEC in the treatment of ovarian cancer.

Ten-year survival for patients with epithelial ovarian cancer treated with consolidation hyperthermic intraperitoneal chemotherapy (331)

<b>Objectives:</b> We aimed to evaluate the long-term efficacy of consolidation hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with epithelial ovarian cancer. <b>Methods:</b> This retrospective study included patients who received consolidation HIPEC at Seoul St. Mary's Hospital between January 1991 and December 2003. Consolidation HIPEC was performed during the second-look operation for patients who had a complete or partial response after primary cytoreductive surgery (CRS) and adjuvant platinum-based chemotherapy. HIPEC was performed by perfusion of 6L of lactated Ringer's solution and paclitaxel 175 mg/m² or carboplatin 350 mg/m² at 43-44°C for 90 minutes. Ten-year progression-free survival (PFS) and overall survival (OS) were analyzed and compared with patients who underwent second-look operation without HIPEC. <b>Results:</b> A total of 87 patients were included. Of these, 44 patients (50.6%) received consolidation HIPEC, and the other 43 (49.4%) received second-look operation only (No HIPEC). The 10-year PFS rate was significantly longer in the HIPEC group compared to the control group (59.1% vs 34.9%, p=0.032), and there was a marginal significance in the 10-year OS rate between the two groups (59.1% vs 37.2%, p=0.054). In a subgroup of patients with stage III, HIPEC group showed significantly longer 10-year PFS and OS rate compared with the control group (PFS: 53.8% vs 14.8%, p=0.001; OS: 38.5% vs 11.1%, p=0.036). Multivariate analysis identified HIPEC as an independent favorable prognostic factor for the 10-year PFS (adjusted HR: 0.49, 95% CI: 0.25-0.96, p=0.039), although not for the 10-year OS (adjusted HR: 0.60, 95% CI: 0.31-1.17, p=0.133). Patients who underwent HIPEC with paclitaxel showed a trend of higher PFS and OS compared with those who underwent HIPEC with carboplatin, although the result was not statistically significant (PFS: adjusted HR: 0.39, 95% CI: 0.13-1.2, p=0.102; OS: adjusted HR: 0.31, 95% CI: 0.03-1.1, p=0.070). Adverse events more common in the HIPEC group included thrombocytopenia, elevated liver enzyme, and wound complications. However, these adverse events were reversible and did not delay subsequent consolidation chemotherapy. <b>Conclusions:</b> The consolidation HIPEC demonstrated a significant improvement in 10-year PFS and a marginally significant improvement in 10-year OS in patients with epithelial ovarian cancer, with acceptable toxicity. Fig. 1

Interval debulking surgery with or without hyperthermic intraperitoneal chemotherapy in advanced-stage ovarian cancer: Single-institution cohort study.

To evaluate the additive effects of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval debulking surgery (IDS) in patients with advanced-stage ovarian cancer. From January 2015 to February 2019, 123 patients with stages IIIC-IV ovarian cancer were treated with neoadjuvant chemotherapy (NAC) followed by IDS with optimal cytoreduction. Forty-three patients received IDS with HIPEC and 80 patients had IDS without HIPEC. The median follow-up period was 34.4 months. No differences in baseline characteristics in patients were found between the two groups. The IDS with HIPEC group had fewer median cycles of chemotherapy (P = 0.002) than the IDS group. The IDS with HIPEC group had a higher rate of high surgical complexity score (P = 0.032) and higher rate of complete resection (P = 0.041) compared to the IDS group. The times to start adjuvant chemotherapy were longer in the IDS with HIPEC group compared to the IDS group (P < 0.001). Postoperative grade 3 or 4 complications were similar in the two groups (P = 0.237). Kaplan-Meier analysis showed that HIPEC with the IDS group had better progression-free survival (PFS) (P = 0.010), while there was no difference in overall survival between the two groups (P = 0.142). In the multivariate analysis, HIPEC was significantly associated with better PFS (HR, 0.60; 95% CI, 0.39 - 0.93). The addition of HIPEC to IDS resulted in longer PFS than IDS without HIPEC not affecting the safety profile. Further research is needed to evaluate the true place of HIPEC in the era of targeted treatments.

Peritoneal Metastases of Colorectal Origin Treated with Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy: The Efficiency of Mitomycin C.

Survival of patients affected by colorectal cancerperitoneal metastases (CRC-PM) can be improved with combined complete cytoreductive surgery (CCRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Two chemotherapeutic agents are mainly used: mitomycin C (MMC) and oxaliplatin. A recent prospective randomized clinical trial showed that oxaliplatin-based HIPEC does notimprove survival compared with CCRS alone. The purpose of our study was to compare the survival effectiveness of MMC versus oxaliplatin-based HIPEC using a homogeneous surgical technique and drug protocol. This retrospective monocentric study included all patients prospectively registered for having undergone CCRS and HIPEC using MMC or oxaliplatin for CRC-PM in Strasbourg University Hospital, France, from December 2004 until December 2019. MMC-basedHIPEC and oxaliplatin-basedHIPEC groups were compared with an inverse probability of treatment weighting. A total of 137 patients were included. Groups were comparable for all baseline characteristics except for peritoneal carcinomatosis index. In the weighted multivariate analysis, disease-free survival (DFS) and peritoneal disease-free survival (PDFS) were significantly higher in the MMC-based HIPEC group compared with the oxaliplatin-based HIPEC group with a hazard ratio of 0.74 (CI 95% 0.56-0.98), p = 0.035 and 0.59 (CI 95% 0.40-0.98), p = 0.0084, respectively. There was no difference in overall survival or postoperative morbidity between groups. These results favor a superiority of MMC for DFS and PDFS in comparison with oxaliplatin in HIPEC after CCRS in treatment with curative intent for CRC-PM.

Prolonged Exposition with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) May Provide Survival Benefit after Cytoreductive Surgery (CRS) in Advanced Primary Epithelial Ovarian, Fallopian Tube, and Primary Peritoneal Cancer.

Simple SummaryThe mainstay of therapy for primary advanced ovarian, fallopian tube, and primary peritoneal carcinoma is cytoreductive surgery (CRS) and platinum-containing chemotherapy. Since the primary and recurrent disease is mainly confined to the peritoneal cavity, intraperitoneal chemotherapy with or without hyperthermia has been evolved in order to improve survival. However, the studies to date are mainly retrospective, nonrandomized, and heterogeneous in terms of patient selection. There are currently only a limited number of reliable data on the role of hyperthermic intraperitoneal chemotherapy (HIPEC), its ideal timing of application, and duration. The aim of this study was to report our single-center experience with CRS + HIPEC involving patients with primary FIGO stage ≥ III B epithelial carcinoma. Hereby, multimodal therapy was feasible with acceptable morbidity and mortality, with no difference in overall survival between interval and upfront surgery. However, prolongation of HIPEC was shown to provide survival benefits regardless of previous administration of chemotherapy.Background: The usage of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gynecological cancers is increasing. Methods: Prospectively collected data of 85 advanced primary ovarian/fallopian tube cancer and peritoneal carcinoma patients of a single center were investigated. Results: A total 48, 37, 62, and 25 patients were enrolled into the HIPEC with/without neoadjuvant chemotherapy (upfront vs. interval) and into the 60 min and 90 min long HIPEC groups, respectively. Better overall survival (OS) was observed in the 90 min HIPEC group (p = 0.0330), compared to the 60 min HIPEC group. Neither OS (p = 0. 2410), disease-specific (p = 0. 3670), nor recurrence-free survival (p = 0.8240) differed between upfront and interval HIPEC. Higher peritoneal carcinomatosis index (PCI) values were associated with worse disease-specific survival (p = 0.0724). Age (p = 0.0416), body mass index (p = 0.0044), PCI (p < 0.0001), the type (p = 0.0016) and duration (p = 0.0012) of HIPEC, and increased perioperative morbidity (p < 0.0041) had the greatest impact on OS. Conclusions: Increasing data support the value of HIPEC in the treatment of advanced ovarian cancer. Ongoing prospective studies will definitively clarify the role and timing of this additional therapeutic approach.