Role Of Hyperthermic Intraperitoneal Chemotherapy Research Articles

The role of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) as second-line debulking in advanced ovarian cancer patients. A meta-analysis

Purpose: Ovarian cancer, as a type of gynecological cancer with one of the highest morbidity and recurrence rates, has been the burning issue for modern research. With new therapeutic methods coming to light, the focus on the promising Hyperthermic Intraperitoneal Chemotherapy (HIPEC) has raised questions about its efficacy on patients’ overall survival (OS) and post-surgical quality of life. Methods: A meta-analysis was performed in order to estimate the role of HIPEC in advanced ovarian cancer, concentrating, among others, on the following quality of life. After thorough research on the PubMed and Cochrane databases, using the terms ‘HIPEC, ovarian cancer’, as well as decoding the results on the last decade, a total of nine articles were selected for this purpose. Results: Data decoding revealed a notorious improvement of OS of the cytoreductive surgery (CRS) plus HIPEC versus the CRS arm at 1, 3, 4 and 5 years respectively; (OR 1.10; 95% CI, 0.85-1.43), (OR 1.53; 95% CI, 1.12-2.10), (OR 1.70; 95% CI, 1.03-2.81), (OR 1.22; 95% CI, 0.77-1.95). At 2 years, the collected data depicted a small worsening in OS (OR 0.92; 95% CI, 0.70-1.19). Conclusion: HIPEC, in spite of its recent innovative nature, has already given positive signs for ovarian cancer therapeutic mapping. Objective of the conducted study focuses on investigating its reflection in advanced stages and recurrent ovarian cancer lesions, respectively.

The Role of Hyperthermic Intraperitoneal Chemotherapy in Uterine Cancer Therapy.

Endometrial cancer and uterine sarcoma represent the two major types of uterine cancer. In advanced stages, both cancer entities are challenging to treat and correlate with a meagre survival and prognosis. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is a form of localized chemotherapy that is heated to improve the chemotherapeutic effect on peritoneal metastases. The aim of the current review is to study the role of HIPEC in the treatment of uterine cancer. A literature review was conducted using the MEDLINE and LIVIVO databases with a view to identifying relevant studies. By employing the search terms "hyperthermic intraperitoneal chemotherapy", "uterine cancer", "endometrial cancer", and/or "uterine sarcoma", we managed to identify 26 studies published between 2004 and 2023. The present work embodies the most up-to-date, comprehensive review of the literature centering on the particular role of HIPEC as treatment modality for peritoneally metastasized uterine cancer. Patients treated with cytoreductive surgery, alongside HIPEC, seem to profit from not only higher survival but also lower recurrence rates. Factors such as the completeness of cytoreductive surgery, the peritoneal cancer index, the histologic subtype, or the applied chemotherapeutic agent, all influence HIPEC therapy effectiveness. In summary, HIPEC seems to represent a promising treatment alternative for aggressive uterine cancer.

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.

Hyperthermic intraperitoneal chemotherapy in platinum-sensitive relapsed epithelial ovarian cancer: The CHIPOR randomized phase III trial.

5510 Background: Standard treatment for patients with first platinum-sensitive relapse of epithelial ovarian cancer (EOC) is based on surgery and second-line systemic chemotherapy (CT). The role of hyperthermic intra-peritoneal chemotherapy (HIPEC) remains uncertain. Methods: The CHIPOR multicentric randomized phase III trial (NCT01376752), conducted in 31 institutions, enrolled patients with a first platinum-sensitive relapse (platinum-free interval of ≥6 months) of EOC. Patients were treated with 6 cycles of platinum and taxane based CT ± bevacizumab, and those amenable to a complete cytoreductive surgery at the end of CT were enrolled and randomly assigned to receive HIPEC (cisplatin 75 mg/m² at 41°C for 60 min) or not. Randomization was performed during complete cytoreductive surgery, stratified by center, surgical outcome (no residual disease vs residual <0.25 cm), chemotherapy-free interval before relapse, and PARP inhibitor use (yes vs no). The primary endpoint was overall survival (OS). The target sample size was 404 evaluable patients, providing 80% power at 5% alpha after 268 deaths. Secondary endpoints included progression-free survival (PFS), peritoneal PFS, patient-reported outcomes, safety, and postoperative morbidity and mortality (≤60 days after surgery). Results: Between May 11, 2011, and May 14, 2021, 415 patients were randomized. Baseline characteristics were balanced between treatment arms. At the data cutoff (Jan 8, 2023), with a median follow-up of 6.2 years, 268 patients (65%) had died. Efficacy results are summarized below. Conclusions: HIPEC significantly improves OS and peritoneal PFS of women with first platinum-sensitive relapse of EOC treated with second-line platinum-based CT followed by secondary complete cytoreductive surgery. Ongoing analyses, including patient reported outcome, BRCA status, bevacizumab exposure, and subsequent therapy, will be presented. Clinical trial information: NCT01376752 . [Table: see text]

DNA Repair Pathway in Ovarian Cancer Patients Treated with HIPEC.

DNA repair pathways are essential for maintaining genome stability, and understanding the regulation of these mechanisms may help in the design of new strategies for treatments, the prevention of platinum-based chemoresistance, and the prolongation of overall patient survival not only with respect to ovarian cancer. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) together with cytoreductive surgery (CRS) and adjuvant systemic chemotherapy is receiving more interest in ovarian cancer (OC) treatment because of the typical peritoneal spread of the disease. The aim of our study was to compare the expression level of 84 genes involved in the DNA repair pathway in tumors and the paired peritoneal metastasis tissue of patients treated with CRS/platinum-based HIPEC with respect to overall patient survival, presence of peritoneal carcinomatosis, treatment response, and alterations in the BRCA1 and BRCA2 genes. Tumors and metastatic tissue from 28 ovarian cancer patients collected during cytoreductive surgery before HIPEC with cisplatin were used for RNA isolation and subsequent cDNA synthesis. Quantitative real-time PCR followed. The most interesting findings of our study are undoubtedly the gene interactions among the genes CCNH, XPA, SLK, RAD51C, XPA, NEIL1, and ATR for primary tumor tissue and ATM, ATR, BRCA2, CDK7, MSH2, MUTYH, POLB, and XRCC4 for metastases. Another interesting finding is the correlation between gene expression and overall survival (OS), where a low expression correlates with a worse OS.

ASO Visual Abstract: Role of Hyperthermic Intraperitoneal Chemotherapy Combined with Cytoreductive Surgery as Consolidation Therapy for Advanced Epithelial Ovarian Cancer.

ASO Visual Abstract: Role of Hyperthermic Intraperitoneal Chemotherapy Combined with Cytoreductive Surgery as Consolidation Therapy for Advanced Epithelial Ovarian Cancer.

Intra-Abdominal Desmoplastic Small Round Cell Tumor (DSRCT) and the Role of Hyperthermic Intraperitoneal Chemotherapy (HIPEC): A Review.

Desmoplastic small round cell tumor is a very rare and highly aggressive soft tissue sarcoma, usually presenting with multiple intra-abdominal tumors in young males. Patients present with advanced disease and the overall survival is dismal. Multiple studies report relatively favorable outcomes with multimodal treatment consisting of chemotherapy, surgery and radiotherapy. If resection is feasible, complete cytoreductive surgery is the cornerstone of surgical treatment. The benefit of hyperthermic intraperitoneal chemotherapy in addition to cytoreductive surgery is unclear, and few studies have evaluated this option. We sought to identify the role of hyperthermic intraperitoneal chemotherapy in patients with intra-abdominal desmoplastic small round cell tumor. Our review of the available literature revealed no clear survival benefit in performing hyperthermic intraperitoneal chemotherapy after cytoreductive surgery.

Role of Hyperthermic Intraperitoneal Chemotherapy Combined with Cytoreductive Surgery as Consolidation Therapy for Advanced Epithelial Ovarian Cancer.

Patients with advanced epithelial ovarian cancer who undergo incomplete surgery followed by six cycles of chemotherapy could benefit from second-look or consolidation cytoreductive surgery (CCRS). The primary goal of this study was to evaluate the overall survival (OS) in patients undergoing complete CCRS and the factors affecting survival. The secondary goal was to study the benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) in these patients. This was a retrospective analysis of 173 patients with CCRS with (n=118) or without (n=55) HIPEC treated at 12 French centers. Only patients having a completeness of cytoreduction (CC)0/1 resection and a minimum of 5 years of follow-up were included. HIPEC was performed systematically for all patients except those treated at the four centers that did not perform HIPEC. The median Peritoneal Cancer Index was 6 (range 0-33). Closed HIPEC was performed in 59 (34.1%) patients and open HIPEC was performed in 56 (32.3%) patients. Grade 3-4 complications occurred in 64 (36.9%) patients. The median OS was 35.67 months (95% confidence interval [CI] 29.8-46.1) and was significantly longer for CCRS+HIPEC (31.4 months without HIPEC and 42.5months with HIPEC; p=0.022). On multivariate analysis, closed HIPEC (hazard ratio [HR] 0.46, 95% CI 0.29-0.73; p<0.001) resulted in a longer OS, and age > 65 years (HR 2.17, 95% CI 1.14-4.11; p=0.018) and bowel resection (HR 1.98, 95% CI 1.27-3.08; p=0.020) led to a shorter OS. On multivariate logistic regression analysis, closed HIPEC (odds ratio 0.18; p=0.001) was associated with a lower risk of dying at 5 years. CCRS was performed with an acceptable morbidity and resulted in good overall survival. The role of HIPEC in addition to CCRS should be evaluated in prospective, randomized studies and the closed technique prospectively compared with the open technique.

Role of HIPEC after Complete Cytoreductive Surgery (CRS) in Peritoneal Recurrence of Platinum-Sensitive Recurrent Ovarian Cancer (OC): The Aim for Standardization at Two Reference Centers for CRS.

This bicentric study evaluated cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for platinum-sensitive recurrent ovarian cancer patients. The data of 88 patients with the first peritoneal recurrence of platinum-sensitive epithelial ovarian cancer who underwent CRS and HIPEC from a prospective HIPEC registry were retrospectively investigated. Endpoints were feasibility, chemotherapeutic compound, time of exposure, complications, and overall survival. The median follow-up was 4.7 years (95%-CI 4.6-5.5). The median age was 55.8 years (IQR: 50.3-66.2). Eighty-four patients (95.5%) had high-grade serous histology. The median peritoneal cancer index was 12.0 (IQR: 7.0-20.5). Sixty-five patients (73.9%) had complete cytoreduction (CCR 0). Thirty-eight patients (43.2%) received HIPEC for 60 min, and fifty patients (56.8%) for 90 min. Eighteen patients (20.5%) had grade III to IV complications. One patient (1.1%) died perioperatively. The overall median survival was 43.1 months (95%-CI 34.1-52.2), and the 5-year survival rate was 39.7%. Only 90 min HIPEC and cisplatin were associated with survival. In well-selected patients with platinum-sensitive recurrent ovarian cancer, survival may correlate with complete CRS and 90 min cisplatin-based HIPEC. We confirmed the results of primary OC studies; therefore, this combination should be used for further analysis in the recurrent situation.

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.

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.

Role of hyperthermic intraperitoneal chemotherapy in combination with an intraperitoneal port system in the treatment of patients with advanced ovarian cancer

Background. The survival rate of patients with ovarian malignancies depends on the prevalence of the tumor process, the volume of surgical treatment, and the size of the residual tumor. At the first stage, an «aggressive» surgical tactic of removing all macroscopically determined tumor foci with subsequent antitumor drug therapy is recommended. However, the results of treatment remain unsatisfactory, which dictates the need to search for new methods of treatment.Objective: to evaluate the effectiveness of implantable port systems for intraperitoneal chemotherapy administration in the treatment of patients with advanced stages of ovarian cancer.Materials and methods. 37 cases of stage IIIC ovarian cancer were studied for the period 2018–2019. At the first stage of treatment, a cytoreductive operation was performed. At the second stage, the patients were randomly randomized into three groups: group 1 (n = 9) – installation of a port system + hyperthermic intraperitoneal chemoperfusion followed by intraperitoneal chemotherapy; group 2 (n = 11) – hyperthermic intraperitoneal chemoperfusion followed by systemic intravenous chemotherapy; group 3 (n = 17) – control group, intravenous administration of antitumor drugs. The observation period is 27 months. In the study groups, the indicators of age distribution, the degree of malignancy of the neoplasm, the volume of the residual tumor, and the relapse-free survival were analyzed.Results. Trends towards differences in progression-free survival were found in all study groups. In group 1, there was no relapse in all patients. In group 2, relapses amounted to 18.2 %, in group 3–23.5 %. G3 ovarian cancer (6 (66.7 %) and 6 (54.5 %) cases, respectively) prevailed in groups 1 and 2; G1 ovarian cancer (9 (52.9 %) cases) prevailed in group 3. Discussion. Features of the chemical composition and method of administration of the drug increase the effectiveness of local exposure to tumor cells. The introduction of cytostatic agents into the abdominal cavity leads to minimal systemic toxicity, which exceeds the results of standard intravenous therapy.Conclusion. An advantage in the relapse-free survival of patients after hyperthermic intraperitoneal chemoperfusion in combination with an implantable port system was found in comparison with standard methods of treatment.

Neoadjuvant chemotherapy in advanced-stage ovarian cancer - state of the art.

Ovarian cancer represents the fifth cause of cancer death among women, carrying one of the worst prognoses among gynaecological malignancies. The need to achieve no residual disease after surgery in order to optimize prognosis of advanced-stage ovarian cancer introduced the idea of neoadjuvant chemotherapy. The present review aims to summarize current state-of-the-art evidence regarding the efficacy and safety of neoadjuvant chemotherapy as well as novel insights regarding the usage of modern therapeutic regimens in the context of neoadjuvant chemotherapy. The last decade has been characterized by the breakthrough scientific evidence that neoadjuvant chemotherapy followed by interval debulking surgery for advanced-stage ovarian cancer may be comparable to primary debulking surgery. Neoadjuvant chemotherapy followed by interval debulking surgery is an acceptable - if not preferable - therapeutic approach in advanced-staged ovarian cancer patients because it is associated with higher optimal debulking surgery, fewer complications, and non-inferior survival outcomes. The addition of bevacizumab to chemotherapy contributes significantly to survival outcomes without causing side effects that outbalance the benefits. Patients with recurrent high-grade serous ovarian cancer and a germline or breast cancer mutation should be offered maintenance olaparib after a response to platinum-based chemotherapy. Finally, the role of hyperthermic intraperitoneal chemotherapy in the context of neoadjuvant chemotherapy remains unjustified.

Prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) for the prevention and control of peritoneal metastasis in patients with gastrointestinal malignancies: a systematic review of randomized controlled trials.

Peritoneal metastasis is associated with poor prognosis, with studies in the literature reporting the survival of peritoneal metastasis without treatment to be three to six months. Hyperthermic intraperitoneal chemotherapy (HIPEC) has shown positive outcomes by improving the prognosis in patients with gastrointestinal malignancies. This systematic review of randomized controlled trials was done to determine the prophylactic role of hyperthermic intraperitoneal chemotherapy in preventing and controlling peritoneal metastasis gastrointestinal origin. Randomized controlled trials published between January 2019 to June 2021 were included. The databases used were MEDLINE (PubMed), EMBASE (Ovid), and the Cochrane library. Cochrane handbook for systematic review of intervention was used to assess the risk of bias in included trials. The results were reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A total of five trials met the inclusion criteria. Two studies were on patients with gastric cancer, and the other three studies were on patients with colorectal cancer. HIPEC was given to a total of 116 gastric cancer patients and 308 colorectal cancer patients. In all the included studies on patients with gastric cancer, the peritoneal recurrence-free survival was significantly higher in the group that received HIPEC. There was no significant improvement in peritoneal-free survival in patients with colorectal cancer who received HIPEC. HIPEC appears to be effective in preventing peritoneal metastasis in patients with locally advanced gastric cancer without minimal postoperative complications. However, in patients with advanced colorectal malignancy, HIPEC does not seem to play a crucial role in preventing and controlling peritoneal metastasis.

Place of hyperthermic intraperitoneal chemotherapy in the armament against pancreatic adenocarcinoma: A survival, mortality and morbidity systematic review.

Pancreatic adenocarcinoma is one of the deadliest types of cancer worldwide, with a 5-year survival rate of 8% despite recent treatment advancements. The present systematic review aimed to investigate the role of hyperthermic intraperitoneal chemotherapy (HIPEC) following surgical resection for pancreatic adenocarcinoma, with or without peritoneal carcinomatosis. A systematic search of the MEDLINE and SCOPUS electronic databases was performed according to PRISMA guidelines. All possible relevant articles published between January 1980 and May 2019 were retrieved using multiple search terms associated with HIPEC and pancreatic adenocarcinoma. The initial search resulted in 1,244 reports, which condensed to 41 reports following screening of titles and abstracts, and subsequently to four reports following full-text thorough examination. The four reports included involved a prospective cohort study of HIPEC use in resectable pancreatic adenocarcinoma, and three retrospective studies of HIPEC use following cytoreductive surgery for peritoneal carcinomatosis due to pancreatic adenocarcinoma, resulting in a total of 47 patients. The overall survival ranged between 2 and 62 months, and the hospital mortality rate was 8.5%. Morbidity (34%) was mainly attributed to anastomotic leak or respiratory failure. Due to the small sample size and low quality of evidence of the included studies, no valid conclusions could be drawn. Therefore, further studies are required to justify the use of HIPEC as an adjuvant therapy in resectable pancreatic adenocarcinoma, while cytoreductive surgery and HIPEC in peritoneal carcinomatosis of pancreatic origin seems not only not useful but also unsafe at this level of evidence.

The Role of Hyperthermic Intraperitoneal Chemotherapy in Pseudomyxoma Peritonei After Cytoreductive Surgery

Studies on the prognostic role of hyperthermic intraperitoneal chemotherapy (HIPEC) in pseudomyxoma peritonei (PMP) are currently not available. To evaluate outcomes after cytoreductive surgery (CRS) and HIPEC compared with CRS alone in patients with PMP. This cohort study analyzed data from the Peritoneal Surface Oncology Group International (PSOGI) registry, including 1924 patients with histologically confirmed PMP due to an appendiceal mucinous neoplasm. Eligible patients were treated with CRS with or without HIPEC from February 1, 1993, to December 31, 2017, and had complete information on the main prognostic factors and intraperitoneal treatments. Inverse probability treatment weights based on the propensity score for HIPEC treatment containing the main prognostic factors were applied to all models to balance comparisons between the CRS-HIPEC vs CRS-alone groups in the entire series and in the following subsets: optimal cytoreduction, suboptimal cytoreduction, high- and low-grade histologic findings, and different HIPEC drug regimens. Data were analyzed from March 1 to June 1, 2018. HIPEC including oxaliplatin plus combined fluorouracil-leucovorin, cisplatin plus mitomycin, mitomycin, and other oxaliplatin-based regimens. Overall survival, severe morbidity (determined using the National Cancer Institute Common Terminology for Adverse Events, version 3.0), return to operating room, and 30- and 90-day mortality. Differences in overall survival were compared using weighted Kaplan-Meier curves, log-rank tests, and Cox proportional hazards multivariable models. A sensitivity analysis was based on the E-value from the results of the main Cox proportional hazards model. Differences in surgical outcomes were compared using weighted multivariable logistic models. Of the 1924 patients included in the analysis (997 [51.8%] men; median age, 56 [interquartile range extremes (IQRE), 45-65] years), 376 were in the CRS-alone group and 1548 in the CRS-HIPEC group. Patients with CRS alone were older (median age, 60 [IQRE, 48-70] vs 54 [IQRE, 44-63] years), had less lymph node involvement (14 [3.7%] vs 119 [7.7%]), received more preoperative systemic chemotherapy (198 [52.7%] vs 529 [34.2%]), and had higher proportions of high-grade disease (179 [47.6%] vs 492 [31.8%]) and suboptimal cytoreduction residual disease (grade 3, 175 [46.5%] vs 117 [7.6%]). HIPEC was not associated with a higher risk of worse surgical outcomes except with mitomycin, with higher odds of morbidity (1.99; 95% CI, 1.25-3.19; P = .004). HIPEC was associated with a significantly better overall survival in all subsets (adjusted hazard ratios [HRs], 0.60-0.68, with 95% CIs not crossing 1.00). The weighted 5-year overall survival was 57.8% (95% CI, 50.8%-65.7%) vs 46.2% (95% CI, 40.3%-52.8%) for CRS-HIPEC and CRS alone, respectively (weighted HR, 0.65; 95% CI, 0.50-0.83; P < .001; E-value, 2.03). Such prognostic advantage was associated with oxaliplatin plus fluorouracil-leucovorin (HR, 0.42; 95% CI, 0.19-0.93; P = .03) and cisplatin plus mitomycin (HR, 0.57; 95% CI, 0.42-0.78; P = .001) schedules. In this cohort study, HIPEC was associated with better overall survival when performed after CRS in PMP, generally without adverse effects on surgical outcomes.

Multicystic peritoneal mesothelioma treated with cytoreductive surgery followed or not by hyperthermic intraperitoneal chemotherapy: results from a large multicentric cohort

Background Multicystic peritoneal mesothelioma (MCPM) is a rare, slowly growing, condition prone to recur after surgery. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) added to complete cytoreductive surgery (CRS) remains controversial and difficult to assess. As patients are mostly reproductive age women, surgical approach, and fertility considerations are important aspects of the management. This observational retrospective review aimed to accurate treatment strategy reflections. Methods The RENAPE database (French expert centers network) was analyzed over a 1999–2019 period. MCPM patients treated with CRS were included. A special focus on HIPEC, mini-invasive approach, and fertility considerations was performed. Results Overall 60 patients (50 women) were included with a median PCI of 10 (4–14) allowing 97% of complete surgery, followed by HIPEC in 82% of patients. A quarter of patients had a laparoscopic approach. Twelve patients (20%) recurred with a 3-year recurrence free survival of 84.2% (95% confidence interval 74.7–95.0). The hazard of recurrence was numerically reduced among patients receiving HIPEC, however, not statistically significant (hazard ratio 0.41, 0.12–1.42, p = 0.200). A severe post-operative adverse event occurred in 22% of patients with five patients submitted to a subsequent reoperation. Among four patients with a childbearing desire, three were successful (two had a laparoscopic-CRS-HIPEC and one a conventional CRS without HIPEC). Conclusion MCPM patients treatment should aim at a complete CRS. The intraoperative treatment options as laparoscopic approach, fertility function sparing and HIPEC should be discussed in expert centers to propose the most appropriate strategy.

Hyperthermic intraperitoneal chemotherapy in ovarian cancer: Qui Bono?

Ovarian cancer is a major cause of cancer related-death in women around the world. Recent statistics on the worldwide cancer burden by the International Agency for the research on Cancer revealed ovarian cancer being both the eighth most frequent malignancy in the west countries. Peritoneal metastasis from ovarian cancer is a major challenge in the clinical management. Despite the evidence of the benefit of Intraperitoneal Chemotherapy in ovarian cancer with peritoneal deposits it has not been widely adopted, mainly due to logistical difficulties and less to the logoregional morbidity as pain. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) in patients during the end of cytoreductive surgery (CRS) is a more tolerable feasible method with potential advantages as drug distribution, combination with hyperthermia and application before tumor regrowth. The aim of this article is to investigate the potential benefits of HIPEC explains the rationale, data of major clinical trials meta-analyses and recent randomized trial are presented and explains the indications patient selection and the best time to applicate of this aggressive logo regional treatment.

The role of hyperthermic intraperitoneal chemotherapy in the treatment of spontaneously ruptured hepatocellular carcinoma: a pilot study.

BackgroundSpontaneous tumor rupture is a distinctive disease pattern in patients with hepatocellular carcinoma (HCC). The application of hyperthermic intraperitoneal chemotherapy (HIPEC) in spontaneously ruptured hepatocellular carcinoma (srHCC) is debatable. Our study aimed to compare the long-term outcomes of srHCC vs. nrHCC and to test the role of postoperative HIPEC in patients with srHCC after hepatectomy.MethodsFrom 2014 to 2018, PSM was performed to compare 57 patients who performed liver resection for srHCC and met the research criteria with 57 nrHCC patients selected from 446 consecutive patients. Then patients with srHCC were divided into two groups according to whether they underwent HIPEC after hepatectomy.ResultsAfter 1:1 PSM, the clinical characteristics of the patients with srHCC and nrHCC were comparable. In terms of long-term outcomes, the nrHCC group had significantly longer OS (P=0.026) and DFS (P<0.001) than the srHCC group. Of the 57 srHCC patients, the HIPEC group showed added complications compared to the non-HIPEC group, including an increased length of hospital stay and higher in-hospital costs. However, there were no significant differences in the metastatic patterns of these recurrent patients, and there was no statistically significant difference in DFS (P=0.28) or OS (P=0.56) between the two groups.ConclusionsThe prognosis of ruptured HCC patients were worse than those of non-ruptured HCC patients. HIPEC may not be a robust treatment for srHCC now.

Role of hyperthermic intraperitoneal chemotherapy in ovarian cancer.

Epithelial ovarian cancer (EOC), has the highest worldwide mortality of all gynecological tumors, in 75% of cases is diagnosed in advanced stages. Despite of treatments with maximal cytoreductive surgery (CRS) and platinum-based chemotherapy (CT), approximately 70% of patients with advancedstage disease relapse within 18 months, given this high number of recurrences, new approaches are needed to improve outcomes for these patients. Hyperthermic intraperitoneal chemotherapy (HIPEC) has fundamentally changed the treatment of patients with ovarian cancer, with complete CRS and locoregional administration of chemotherapy. The purpose of this review is to find the most relevant, reliable published evidence of the use of HIPEC in ovarian cancer, together with an overview of peritoneal carcinomatosis (PC), procedures, therapeutic approaches in first-line and recurrent disease, the benefit of hyperthermia, selection of the ideal patient for the HIPEC procedures as well to analyze the disease free survival (DFS), morbidity, mortality and overall survival (OS) in patients with ovary cancer. So far, the small amount of evidence points favorably to the use of CRS and HIPEC as a first line of therapy, but more prospective randomized trials are needed to officially adopt this procedure as a standard of care, additionally patients need to know this option exists.