Effect Of Hyperthermic Intraperitoneal Chemotherapy Research Articles

Comment on 'Effect of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) on survival and recurrence rates in advanced gastric cancer - a systematic review and meta-analysis'.

Comment on 'Effect of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) on survival and recurrence rates in advanced gastric cancer - a systematic review and meta-analysis'.

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.

Investigation of the effectiveness of hyperthermic intraperitoneal chemotherapy in experimental colorectal peritoneal metastasis model.

In our study, we aimed to (1) create a peritoneal metastasis (PM) model in nude mice, administer intraperitoneal chemotherapy using the peritoneal infusion pump we developed in this model, and (2) compare the efficacy of intraperitoneal chemotherapy using various drugs at different temperatures. The peritoneal metastasis model was established in nude mice using the CC531 colon carcinoma cell line. Models with peritoneal metastasis (PM) were randomized into four groups of seven animals each: Group 1, control group (n=7); Group 2, normothermic intraperitoneal chemotherapy (NIPEC) with mitomycin C(MMC) (n=7); Group 3, hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin C (n=7), and Group 4, NIPEC with 5-fluorouracil (5-FU). Tumor development was achieved in all animals. While the tumor burden decreased significantly in the treatment Group 3 (p=0.034), no significant difference was found in the other groups. In the PM mouse model, hyperthermic intraperitoneal administration of MMC had the highest tumoricidal effect. Our PM model provided a good opportunity to examine the efficacy of HIPEC and intraperitoneal infusion pump (IPIP). In future studies, we plan to evaluate efficacies of different drugs in the PM models we have created.

Effectiveness of Hyperthermic Intraperitoneal Chemotherapy Associated with Cytoreductive Surgery in the Treatment of Advanced Ovarian Cancer: Systematic Review and Meta-Analysis.

The use of hyperthermic intraperitoneal chemotherapy (HIPEC) as a treatment for epithelial ovarian cancer remains controversial. Our study aims to analyze the overall survival and disease-free survival for the use of HIPEC as a treatment for advanced epithelial ovarian cancer after neoadjuvant chemotherapy. A systematic review and meta-analysis was carried out using PubMed, Cochrane, Web of Science, and ClinicalTrials.gov. A total of six studies were used, comprising a total of 674 patients. The results of our meta-analysis of all studies analyzed together (observational and randomized controlled trials (RCT)) did not achieve significant results. Contrary to the OS (HR = 0.56, 95% IC = 0.33-0.95, p = 0.03) and DFS (HR = 0.61, 95% IC = 0.43-0.86, p < 0.01) of the RCT analyzed separately, a clear impact on survival was suggested. The subgroup analysis showed that studies making use of higher temperatures (≥42 °C) for a shorter period of time (≤60 min) achieved better results for both OS and DFS, as well as the use of cisplatin as the form of chemotherapy in HIPEC. Moreover, the use of HIPEC did not increase high-grade complications. The addition of HIPEC to cytoreductive surgery demonstrates an improvement in OS and DFS for patients with epithelial ovarian cancer in advanced stages, without an increase in the number of complications. The use of cisplatin as chemotherapy in HIPEC obtained better results.

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.

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.

Effect of hyperthermic intraperitoneal chemotherapy in combination with cytoreductive surgery on the prognosis of patients with colorectal cancer peritoneal metastasis: a systematic review and meta-analysis

BackgroundPeritoneal metastasis often occurs in patients with colorectal cancer peritoneal metastasis, and the prognosis is poor. A large body of evidence highlights the beneficial effects of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on survival, but to date, there is little consensus on the optimal treatment strategy for patients with colorectal cancer peritoneal metastasis. The purpose of this study is to evaluate the impact of CRS + HIPEC on survival and provide reference for the treatment of patients with colorectal cancer peritoneal metastasis.MethodsThis systematic review and meta-analysis is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The PubMed, Embase, Cochrane, Web of Knowledge, and ClinicalTrials.gov databases were screened from inception of the review to March 11, 2022. Ten studies were included in qualitative and quantitative analysis.ResultsA total of 3200 patients were enrolled in the study, including 788 patients in the CRS and HIPEC groups and 2412 patients in the control group, of which 3 were randomized controlled trials and 7 were cohort studies. The 3 randomized controlled studies were of high quality, and the quality scores of the 7 cohort studies were all 7 or above, indicating high quality. The results showed that the OS of CRS + HIPEC group was higher than that of control group (HR: 0.53, 95% CI: 0.38–0.73; P < 0.00001, I2 = 82.9%); the heterogeneity of the studies was large. The subgroup analysis showed that the OS of CRS and HIPEC group was higher than that of PC group (HR: 0.37, 95% CI: 0.30–0.47; P = 0.215, I2 = 31%) and higher than that in CRS group (HR: 0.73, 95% CI: 0.49–1.07; P = 0.163, I2 = 44.8%); the heterogeneity of the studies was low. In the OPEN group, the OS of THE CRS and HIPEC groups was higher than that in the control group (HR: 0.51, 95% CI: 0.38–0.70; P = 0.353, I2 = 3.9%); OPEN group showed lower heterogeneity. The OS of 60–100-min group was higher than that in the control group (HR: 0.65, 95% CI: 0.49–0.88; P = 0.172, I2 = 37.4%); the heterogeneity of the studies was low. Sensitivity analysis showed that there was no significant difference in the results of the combined analysis after each study was deleted. The results of publication bias showed that the P-value of Egger and Begg tests was 0.078 > 0.05, indicating that there is no publication bias.ConclusionsCRS + HIPEC can improve the survival rate of patients with colorectal cancer peritoneal metastasis

Anastomotic leakage after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal cancer

BackgroundAnastomotic leakage (AL) after colorectal surgery is well-researched, yet the effect of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) after Cytoreductive Surgery (CRS) is unclear. Assessment of risk factors in these patients may assist surgeons during perioperative decision making. MethodsThis was a single-center, retrospective study of patients who underwent CRS-HIPEC for colorectal peritoneal metastases. Main outcome measures were anastomotic leakage and associated morbidity. ResultsAL was observed in 17 of the 234 (7.3%) anastomoses in 17 of the total of 165 (10.3%) of patients. No association was observed between the number and location of anastomoses and AL, although only one in 87 small bowel anastomoses showed leakage. The only factor associated with AL was administration of bevacizumab within 60 days prior to surgery with an odds ratio (OR) of 6.13 (1.32–28.39), P = 0.03. Deviating stomata were not statistically protective of increased morbidity, although more AL occurred in the patients with colocolic and colorectal anastomoses when no concomitant deviating stoma was created. Deviation stomata were reversed in 52.6%, and no AL was observed after stoma reversal. ConclusionThe overall AL rate of CRS-HIPEC is comparable to colorectal surgery, and there is no cumulative risk of multiple anastomoses – especially in the case of small bowel anastomoses. Deviating stomata should be considered in patients with colocolic or colorectal anastomosis, although there is a significant chance that the stoma will not be reversed in these patients. Due to increased AL-risk surgeons should be aware of previous bevacizumab treatment, and plan the CRS-HIPEC at least 60 days after the treatment-day.

Hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin induces distinct transcriptomic changes in ovarian tumor and normal tissues

ObjectiveTo determine the effect of hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin on the transcriptomic profiles of normal and ovarian cancer (OC) tissues. MethodsNormal and tumor samples from four OCs were prospectively collected pre- and immediately post-HIPEC treatment and subjected to RNA-sequencing. Differential gene expression, gene ontology enrichment and pathway analyses were performed. Heat shock protein and immune-response protein expression was assessed using protein arrays and western blotting. ResultsRNA-sequencing revealed 4231 and 322 genes significantly differentially expressed between pre- and post-treatment normal and OC tissues, respectively (both adjusted p-value <0.05). Gene enrichment analyses demonstrated that the most significantly upregulated genes in normal tissues played a role in immune as well as heat shock response (both adjusted p < 0.001). In contrast, HIPEC induced an increased expression of primarily heat shock response and protein folding-related genes in tumor tissues (both adjusted p < 0.001). HIPEC-induced heat shock protein (HSP) expression changes, including in HSP90, HSP40, HSP60, and HSP70, were also observed at the protein level in both normal and tumor tissues. ConclusionsHIPEC with carboplatin resulted in an upregulation of heat shock-related genes in both normal and tumor tissue, with an additional immune response gene induction in normal and protein folding in tumor tissue. The findings of our exploratory study provide evidence to suggest that HIPEC administration may suffice to induce gene expression changes in residual tumor cells and raises a biological basis for the consideration of combinatorial treatments with HSP inhibitors.

Impact of hyperthermic intraperitoneal chemotherapy on genomic heterogeneity of peritoneal metastases in stage IV gastroesophageal adenocarcinoma.

312 Background: Programmed death ligand 1 (PD-L1) expression and tumor mutational burden (TMB) are potential biomarkers for response to therapy. Heterogeneity of PD-L1 and TMB has been demonstrated in gastroesophageal adenocarcinoma (GEA) in response to systemic chemotherapy. With the increased use of hyperthermic intraperitoneal chemotherapy (HIPEC) for GEA peritoneal metastases (PM), we aimed to determine the effects of HIPEC on genomic heterogeneity of PM. Methods: This is a retrospective review of a prospectively maintained database of patients with stage IV GEA who underwent iterative laparoscopic HIPEC (mitomycin C 30 mg + cisplatin 200 mg, 60 minutes) between 2017 and 2021. PD-L1 status and TMB levels were reviewed from peritoneal tumor specimens collected prior to each HIPEC. PD-L1 status was defined as positive if combined positive score (CPS) was 1 or greater using the 22C3 pharmDx assay. TMB levels were defined as low, intermediate, or high for up to 5, 5 to 15, or over 15 mutations per megabase (m/MB), respectively. Potentially actionable and biologically relevant variants were reviewed, as well as overall survival, defined as time from diagnosis with stage IV disease to death from any cause. Results: 16 patients completed at least one HIPEC during the study period. Median age was 55.5 years (range 43-79), 50% were female, and 62.5% were Caucasian. All patients received at least one line of systemic chemotherapy after stage IV diagnosis and prior to first HIPEC. Median peritoneal cancer index at first HIPEC was 15 (range 3-39). Three patients completed only one HIPEC. Of the 13 who completed at least two HIPECs, 5 had sufficient tumor tissue for genomic analysis at two timepoints. Of those 5 patients, one exhibited a change in PD-L1 expression from positive to negative after HIPEC, and one exhibited an increase in TMB from low to intermediate. All 5 patients exhibited a change in the profile of potentially actionable or biologically relevant genetic variants, including gain or loss of mutations in DNA repair genes (RAD51), proto-oncogenes (MET), and tumor suppressor genes (ERBB3, IRS2). Median overall survival amongst the full cohort was 27.4 months, with median follow-up of 26.1 months. Overall survival was higher amongst those who underwent at least 2 HIPECs compared to only one, but this was not statistically significant. Conclusions: Amongst our cohort, only one patient exhibited a change in PD-L1 expression and one in TMB after HIPEC. However, HIPEC was associated with a change in genetic variant profiles in all evaluable patients. If confirmed in larger studies, this temporal genomic heterogeneity could inform the role of PD-L1, TMB, and other genetic variants as predictive biomarkers for therapy after HIPEC. Iterative laparoscopic HIPEC warrants further investigation as a treatment option after systemic therapy for GEA with peritoneal metastases.

Ascites and Serial Plasma Circulating Tumor DNA for Predicting the Effectiveness of Hyperthermic Intraperitoneal Chemotherapy in Patients With Peritoneal Carcinomatosis.

PurposeWe investigated the value of ascites and serial plasma circulating tumor DNA (ctDNA) for predicting response to hyperthermic intraperitoneal chemotherapy (HIPEC), monitoring tumor burden, and predicting prognosis in patients with peritoneal carcinomatosis (PC).Experimental DesignIn this observational study, 19 patients with PC were enrolled. Serial plasma ctDNA was analyzed using next-generation sequencing. The molecular tumor burden index (mTBI) was used to detect ctDNA, and concurrent changes in the dominant clone variant allele frequency (VAF) and common tumor markers were used as controls. The correlation between ascites and plasma ctDNA comutated genes was expressed by VAF. The overall response rate (complete response + partial response) after HIPEC was determined. Ascites progression-free survival (PFS) and overall survival (OS) were determined, and potential correlations between these outcomes and change in mTBI (△mTBI), change in sum-VAF (△sum-VAF), dominant close VAF, and tumor markers were assessed.ResultsThe overall response rate at 1 month after HIPEC was 100%. The △mTBI (r = 0.673; P = 0.023) and △sum-VAF (r = 0.945; P <0.001) were significantly positively correlated with ascites PFS; these correlations were stronger than those of the dominant clone VAF (r = 0.588; P = 0.057) and tumor markers in the same period (r =0.091; P = 0.790). Patients with a low baseline mTBI (<0.67) demonstrated significantly longer ascites PFS (P = 0.003; HR = 0.157; 95% CI: 0.046–0.540) and OS (P = 0.017; HR = 0.296; 95% CI: 0.109–0.804) than those with a high baseline mTBI (≥0.67). Consistent mutations were detected in plasma and ascites (r = 0.794; P = 0.001).ConclusionA real-time serial plasma ctDNA assay accurately reflected tumor burden. The △mTBI and △sum-VAF can be used as predictors of HIPEC efficacy in patients with PC. A high baseline mTBI may be a negative risk factor for prognosis.

Does Platelet-Rich Plasma (PRP) Improve Colonic Anastomotic Healing in Rats Undergoing Cisplatin-Paclitaxel-Based HIPEC?

Hyperthermic intraperitoneal chemotherapy (HIPEC) causes delays in wound healing. Platelet-rich plasma (PRP) gel has been shown to be effective in facilitating wound healing. We examined the effect of PRP gel on the healing of colonic anastomosis in rats that received HIPEC. Twenty-four rats were subdivided into three groups. In group 1, the rats only underwent colonic anastomosis. In group 2, the rats underwent colonic anastomosis and cisplatin-paclitaxel-based HIPEC. In group 3, the rats underwent colonic anastomosis and cisplatin-paclitaxel-based HIPEC. Afterwards, PRP gel was administered to the colonic anastomosis region. The rats were sacrificed on the 7th postoperative day, the anastomotic bursting pressure (ABP) was recorded, and tissue samples were taken from the anastomotic line. Compared to that in group 2, ABP was higher in group 1 and group 3 (p= 0.002 and 0.048, respectively). Tissue hydroxyproline levels were higher in group 1 (p= 0.001) and group 3 (p = 0.043) than in group 2. Histopathological evaluation revealed a significant decrease in fibroblast activity in group 2 compared to that in group 1 (p= 0.006), with no significant difference between group 3 and group 1 (p= 0.585). Collagen accumulation was significantly lower in group 2 than in group 1 and group 3 (p= 0.001 and p= 0.019, respectively). PRP gel application may aid wound healing by increasing colon ABP, tissue fibroblast activity and collagen accumulation; therefore, its use may reduce the cytotoxic effects of HIPEC and facilitate the anastomotic wound healing process.

Expression of Heat Shock Protein 105b in Adenocarcinoma of Esophagogastric Junction and Its Relation with Effect of Hyperthermic Intraperitoneal Chemotherapy

Expression of Heat Shock Protein 105b in Adenocarcinoma of Esophagogastric Junction and Its Relation with Effect of Hyperthermic Intraperitoneal Chemotherapy

Direct and indirect anticancer effects of hyperthermic intraperitoneal chemotherapy on peritoneal malignancies (Review).

The successful application of hyperthermic intraperitoneal chemotherapy (HIPEC) illustrates its antitumor activity against primary malignances and peritoneal metastases. Although the specific underlying molecular mechanisms remain unclear, increasing evidence suggest that HIPEC directly and indirectly inhibits tumor growth, and prolongs overall survival in both hyperthermic and chemotherapeutic manners. To demonstrate the superiority and limitations of such a therapeutic regimen, the present review focuses on the biological and immunological anticancer mechanisms of HIPEC. In addition, the potential combination of HIPEC with other therapies is discussed, as well as its potential to prolong the overall survival time of patients with peritoneal malignancies.

Gastric Signet Ring Cell Carcinoma: Current Management and Future Challenges.

Recent advances in the epidemiology, pathology, molecular mechanisms, and combined modality therapy (CMT) fields have shown that gastric signet ring cell carcinoma (GSRC) should be considered a distinct cancerous entity. Clinical management of this cancer is challenging, with chemoradioresistance and poor outcomes in advanced stages. Pathological and molecular sets of GSRC demonstrate different features of poor cohesion and differentiation according to the WHO, Japanese Gastric Cancer Association, and Laurén classifications. These features also result in poor response to adjuvant and neoadjuvant chemoradiotherapy. Certain studies of GSRC showed the disputed effectiveness of hyperthermic intraperitoneal chemotherapy and immunotherapy. Our aim was to discuss how an improved understanding of these therapeutic benefits may provide better treatment selection for patients, and therefore improve survival. The challenges in the new understanding of GSRC in routine practice and pathology, and the current limitations of treatment will also be discussed.

Primary cytoreductive surgery with or without Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for FIGO stage III epithelial ovarian cancer: The OVHIPEC-2 trial in progress.

TPS6100 Background: The addition of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to interval cytoreductive surgery improves recurrence-free and overall survival in patients with FIGO stage III ovarian cancer who are ineligible for primary cytoreductive surgery due to extensive intraperitoneal disease. The effect of HIPEC remains undetermined in patients who are eligible for primary cytoreductive surgery. We hypothesize that the addition of HIPEC to a complete or near-complete (residual disease ≤2.5 mm) primary cytoreductive surgery improves overall survival in patients with FIGO stage III ovarian cancer. Methods: This international, randomized, open-label, phase III trial enrolls patients with newly diagnosed, histological proven FIGO stage III epithelial ovarian, fallopian tube, or primary peritoneal cancer. Patients with resectable umbilical, spleen or local bowel lesions may be included. Following complete or near-complete primary cytoreduction, patients are intra-operatively randomized (1:1) to receive HIPEC or no HIPEC. Patients in both study arms will receive six courses of adjuvant carboplatin-paclitaxel and maintenance PARP-inhibitor or bevacizumab according to current guidelines. The primary endpoint is overall survival. To detect a Hazard Ratio of 0.67 in favor of HIPEC, 200 overall survival events are required. Assuming that accrual will be completed in 60 months, and 12 months additional follow-up, 538 patients need to be randomized. All randomized patients will be included in the analysis for overall survival according to the intention to treat principle. Pre-specified subgroup analyses will be performed based on stratification factors (peritoneal cancer index at start of surgery, completeness of surgery), histologic subtype (high-grade serous versus other), and BRCA mutation (BRCA1/2 mutation versus wildtype). Secondary endpoints are recurrence-free survival, time to first subsequent anticancer treatment, and treatment related complications and toxicity. Exploratory endpoints are time to second subsequent anticancer treatment, health-related quality of life, and cost-effectiveness. The Institutional Review Board of the Netherlands Cancer Institute approved the trial, which is actively enrolling patients since January 2020. Clinical trial information: NCT03772028.

Clinical features and surgical outcomes of major urological interventions during cytoreductive surgery and hyperthermic intraperitoneal chemotheraphy.

Background:Urinary system resections and reconstructions are needed in peritoneal carcinomatosis due to abdominal malignancies. The effect of hyperthermic intraperitoneal chemotherapy on these urological procedures after reconstruction remains uncertain. The aim of the study is to evaluate major urological interventions during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in complex abdominal malignancies with peritoneal carcinomatosis.Methods:Forty-four cases underwent surgical intervention related to the urinary system among 208 cases who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy because of peritoneal carcinomatosis. Urinary system procedures performed in these patients (radical-partial cystectomy, partial ureter resection ureteroneocystostomy, ureteroureterostomy, nephrectomy) were evaluated in terms of postoperative morbidity–mortality and survival.Results:Urinary system resections were performed during cytoreductive surgery in a total of 44 cases. The mean age was 54 years (20–73). Patients were diagnosed with peritoneal carcinomatosis due to colorectal cancer in 21 (47.8%), ovarian cancer in nine (20.4%), sarcomatosis in five (11.4%), cervical cancer in four (9%) and other cancers (mesothelioma, uterus, breast, gastric) in five (11.4%) cases. Total nephrectomy was performed in three cases and partial nephrectomy in one case. Cystectomy was performed in 21 cases; 16 of these were partial and five were total cystectomies. Ureteroureterocystostomy with double J was performed in four cases and ureteroneocystostomy in 12 cases. While Clavian–Dindo grade 3–4 complications were seen in nine cases (20.4%), three cases (6.8%) became exitus during the first 30-day follow-up.Conclusions:Although urinary system involvements have been regarded as inoperable in the past, we think that with adequate experience radical urinary interventions performed in suitable patients can be carried out with acceptable morbidity and mortality as seen in our series.

Hyperthermic intraperitoneal chemotherapy for ovarian cancer: The heat is on.

Patients with advanced epithelial ovarian cancer have a high incidence of peritoneal disease recurrence despite maximal efforts to surgically remove all visible tumor plus intravenous chemotherapy. The administration of intraperitoneal chemotherapy that specifically targets the peritoneal surface has been investigated in previous trials, but questions about the design of these studies has prevented this treatment from being widely adopted in clinical practice. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a single intraoperative approach that also targets the peritoneal surface. A randomized phase 3 trial showed significant benefit in recurrence-free and overall survival when HIPEC was added to interval cytoreductive surgery (CRS) in patients who were not eligible for primary surgery because of the extent of their disease(OVHIPEC trial; NCT00426257). The trial showed no important differences in toxicity or patient-reported outcomes between the study groups. The extent of surgery and the number of bowel resections were also similar between the 2 study groups, and the effect of HIPEC was homogeneous across the levels of predefined and post hoc subgroups. Nevertheless, the design and the results of the OVHIPEC trial were critically assessed, and this resembles the reluctance to adopt the positive results of the earlier intraperitoneal chemotherapy studies. This overview discusses the design and results of the OVHIPEC trial. The evidence that is currently available points to a clinically relevant and cost-effective benefit of HIPEC added to interval CRS for patients with stage III ovarian cancer who are not eligible for primary surgery. Ongoing collaborative research will provide further evidence regarding the role of HIPEC in ovarian cancer.

Effect of hyperthermic intraperitoneal chemotherapy for gastric cancer patients: a meta-analysis of the randomized controlled trials.

ObjectiveTo determine the effectiveness and safety of hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with advanced gastric cancer and peritoneal metastases.MethodsPubMed®, CNKI, Web of Science, VIP and WANFANG databases were searched to identify randomized controlled trials (RCTs) that examined the effect of HIPEC on survival, clinical response and adverse events. Patients with advanced gastric cancer and peritoneal metastases were divided into an experimental group and a control group. The statistical results are presented as relative ratio (RR), mean difference (MD) and 95% confidence interval (CI).ResultsTwenty-one RCTs met the inclusion criteria (n = 1674 patients). Meta-analysis showed that the 3-year survival rate was significantly higher in the HIPEC group than in the control group (RR 1.61; 95% CI 1.43, 1.82) and the complete response rate was significantly higher in the HIPEC group than in the control group (RR 2.35; 95% CI 1.67, 3.31). HIPEC was also beneficial in terms of decreased CEA (MD −1.79; 95% CI −2.22, −1.35). There was no significant difference in the rate of adverse reactions (RR 1.00; 95% CI 0.87, 1.14).ConclusionsHIPEC had a beneficial effect on 3-year survival rate and complete response in patients with advanced gastric cancer and peritoneal metastases.

Comparative effectiveness of hyperthermic intraperitoneal chemotherapy for gastric cancer: A systematic review and network meta-analysis protocol: Erratum.

Comparative effectiveness of hyperthermic intraperitoneal chemotherapy for gastric cancer: A systematic review and network meta-analysis protocol: Erratum.