Administration Of Hyperthermic Intraperitoneal Chemotherapy Research Articles

Phase 1 trial of same day cytology to guide the use of HIPEC.

Peritoneal metastases from gastrointestinal or gynecologic malignancy are a prominent part of the natural history of these diseases. Peritoneal metastases, if not effectively treated, will result in a decreased survival and cause an impaired quality of life. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment specifically designed to combat peritoneal metastases. A group of patients who, from a theoretical perspective, may benefit from HIPEC are those patients with a positive peritoneal cytology. In order to identify these patients at the time of a surgical intervention, a same day cytology is to be performed. The result of this test is to be available at or before the completion of the cancer resection. If the cytology is positive, the patient immediately becomes a candidate for HIPEC. The HIPEC will be of maximal value if a complete cytoreduction, as judged by the surgeon, has been possible. This phase 1 trial is to demonstrate that the Surgical Oncology Service, the Department of Pathology, the Pharmacy and the Operating Room personnel can co-ordinate a phase 1 protocol to successfully complete the same day cytology with an efficient delivery of HIPEC. A standardized plan for consent, cytology collection, preparation of the specimen, reading of the specimen, reporting the results in a timely manner facilitates the administration of HIPEC in peritoneal cytology positive patients. Successful completion of these requirements is a positive result for this study and allows for future protocols to be generated. Successful completion of the same day cytology phase 1 protocol will allow the efficacy, safety, and efficiency of this plan of patient management to be evaluated.

Expanding the Use of HIPEC in Ovarian Cancer at Time of Interval Debulking Surgery to FIGO Stage IV and After 6 Cycles of Neoadjuvant Chemotherapy: A Prospective Analysis on Perioperative and Oncologic Outcomes

BackgroundRandomized data on patients with FIGO stage III ovarian cancer receiving ≤ 3 cycles of neoadjuvant chemotherapy (NACT) showed that hyperthermic intraperitoneal chemotherapy (HIPEC) after interval debulking surgery (IDS) improved patient’s survival. We assessed the perioperative outcomes and PFS of FIGO stage IV and/or patients receiving up to 6 cycles of NACT undergoing IDS+HIPEC.MethodsProspectively collected cases from January 1, 2019 to July 31, 2022 were included. Patients underwent HIPEC if: age ≥ 18 years but < 75 years, body mass index ≤ 35 kg/m2, ASA score ≤ 2, FIGO stage III/IV epithelial disease treated with up to 6 cycles of NACT, and residual disease < 2.5 mm.ResultsA total of 205 patients were included. No difference was found in baseline characteristics between FIGO Stage III and IV patients, whereas rate of stable disease after NACT (p = 0.004), mean surgical complexity score at IDS (p = 0.001), and bowel resection rate (p = 0.046) were higher in patients undergoing delayed IDS. A lower rate of patients with at least one G3–G5 postoperative complications was observed in FIGO stage IV versus FIGO stage III disease (5.3% vs. 14.0%; p = 0.052). This difference was confirmed at multivariable analysis (odds ratio [OR] 0.24; 95% confidence interval [CI] 0.07–0.80; p = 0.02), whereas age, SCS, bowel resection, and number of cycles did not affect postoperative complications. No difference in PFS was identified neither between FIGO stage III and IV patients (p = 0.44), nor between 3 and 4 versus > 4 cycles of NACT (p = 0.85).ConclusionsBecause of the absence of additional complications and positive survival outcomes, HIPEC administration can be considered in selected FIGO stage IV and patients receiving > 4 cycles of NACT.

Hyperthermic Intraperitoneal Chemotherapy (HIPEC), Oncological Outcomes and Long-Term Survival among Patients with Gastric Cancer and Limited Peritoneal Disease Progression after Neoadjuvant Chemotherapy.

The role of surgery in stage IV gastric cancer with peritoneal metastasis (PM) remains unclear. The objective of the current single-center study was to define the impact of gastrectomy with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on outcomes among Central European GC patients with limited peritoneal disease progression after neoadjuvant chemotherapy (NAC). Patients with histologically confirmed GC who underwent curative-intent multimodal treatment between 2013 and 2023 were included. Patients without adenocarcinoma, who did not undergo gastrectomy, had early (cT1) or metastatic GC at the time of initial diagnosis, who underwent multivisceral resection, incomplete cytoreduction or palliative care, died before planned curative-intent treatment, or had incomplete clinical or pathological missing information were excluded. A total of 74 patients who underwent curative-intent treatment for GC with PM were included in the final analytic cohort. Patients who underwent gastrectomy with CRS+HIPEC were less likely to achieve TOO (CRS+HIPEC: 28% vs. CRS: 57.1%, p = 0.033) compared with individuals after CRS alone. Specifically, patients who underwent gastrectomy with CRS+HIPEC had a higher likelihood of postoperative complications (CRS+HIPEC: 48% vs. CRS: 20.4%, p = 0.018) and longer hospital LOS (median, CRS+HIPEC: 12 vs. CRS: 10, p = 0.019). While administration of HIPEC did not impact long-term survival (median OS, CRS+HIPEC: 16 months vs. CRS: 12 months, p = 0.55), postoperative complications (median OS, CCI < 30:16 months vs. CCI > 30:5 months, p = 0.024) and ICU stay (median OS, no ICU stay: 16 months vs. ICU stay: 5 months, p = 0.008) were associated with worsened long-term survival among GC patients with PM. Data from the current study demonstrated a lack of survival benefit among advanced GC patients with PM undergoing gastrectomy with CRS+HIPEC when compared with individuals after gastrectomy with CRS alone. Administration of perioperative chemotherapy and achievement of TO failed to withstand the peritoneal disease progression during NAC.

Intraoperative metabolic changes associated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

BackgroundCytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) causes considerable hemodynamic, respiratory, and metabolic changes during the perioperative period.ObjectivesTo evaluate metabolic changes associated with this procedure. Understanding perioperative factors and their association with morbidity may improve the perioperative management of patients undergoing this treatment.MethodsA retrospective review of a prospectively maintained database was performed. All consecutive unselected patients who underwent CRS plus HIPEC between January 2018 and December 2020 (n = 219) were included.ResultsThe mean age was 58 ± 11.7 years and 167 (76.3%) were female. The most frequent histology diagnosis was serous ovarian carcinoma 49.3% (n = 108) and colon carcinoma 36.1% (n = 79). Mean peritoneal cancer index was 14.07 ± 10.47. There were significant variations in pH, lactic acid, sodium, potassium, glycemia, bicarbonate, excess bases, and temperature (p < 0.05) between the pre-HIPEC and post-HIPEC periods. The closed HIPEC technique resulted in higher levels of temperature than the open technique (p < 0.05). Age, potassium level post-HIPEC potassium level, and pre-HIPEC glycemia were identified as prognostic factors for morbidity in multivariate analysis.ConclusionThe administration of HIPEC after CRS causes significant changes in internal homeostasis. Although the closed technique causes a greater increase in temperature, it is not related to higher morbidity rates. The patient’s age, post-HIPEC potassium level, and pre-HIPEC glycemia are predictive factors for morbidity.

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.

Hyperthermic Intraperitoneal Chemotherapy and Recirculation with CO2: A Safe Technique.

Introduction: Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) has evolved as a treatment for peritoneal carcinomatosis in various tumors after a careful and complete cytoreductive surgery, and it demonstrated much better and longer survival than more traditional therapeutic schemas. Our objective has been to examine the safety, efficacy and survival achieved with closed technique with CO2-agitation system Combat PRS® (Peritoneal Recirculation System: PRS). To achieve this, we compared the appearance of adverse events, mortality and survival with the described using classic techniques (open, closed without CO2-agitation) for the treatment of selected patients with peritoneal carcinomatosis; Materials and methods: We studied overall survival, disease-free survival and safety (morbidity and mortality) of the administration of HIPEC through a closed method technique with CO2 recirculation (Combat PRS®) in 482 patients from 11 Spanish hospitals; Results: The mortality of our technique (1.66%) was similar to other published techniques (open, closed). Morbidity exhibited a 9.96% rate of Clavien-Dindo (CD) III/IV complications in 482 patients, which was lower than in other series. Survival (overall survival (OS) and disease-free survival (DFS)) was similar to previously published results: 86% 1y-OS, 54% 3y-OS, 77% 1y-DFS and 31% 3y-DFS; Conclusion: The procedure with closed PRS with CO2 agitation is as safe as standard open and closed procedures for the administration of HIPEC after complete cytoreductive surgery, with similar and very low mortality (1.66%) and lower morbidity (9.96% CD III and IV in our series vs range of 20–40% in the majority of different series); only Kusamura had similar results, with 12% in 205 patients, using the closed technique without CO2 agitation).

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis from Urothelial Origin: a Case Report and Literature Review.

Urothelial carcinomas (UC) are the fourth most common tumours. Approximately, 50% of patients with invasive bladder cancer relapse after radical cistectomy (RC). In this report, we present the case of peritoneal carcinomatosis from bladder UC treated with cytoreductive surgery plus the administration of hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). A 34-year-old woman diagnosed with high-grade bladder cancer with peritoneal recurrence in 2017. She underwent cytoreductive surgery followed by HIPEC with mitomycin C. Histopathological results showed metastases from UC in the left ovary and right diaphragmatic peritoneum. In 2021, the patient underwent surgery after treatment with atezolizumab for abdominal wall recurrence. Today, the patient is alive and free of tumor recurrence 12months after the last surgery. Despite advances in surgical technique and patient selection, the risk of relapse remains high among patients with muscle-invasive bladder cancer. We face the case of a young female patient with local, peritoneal, and lymphatic recurrence of bladder cancer after RC who had a partial response to chemotherapy. The possibility of CRS + HIPEC is offered by the surgical oncology unit, referent in the management of peritoneal carcinomatosis. Surgery is capable of resecting residual tumor in patients with a partial response or who have been erroneously underdiagnosed. CRS + HIPEC might be a valid option to be considered in well-selected patients and to be performed in reference units. There is a need for more collaborative clinical trials and prospective studies addressing the role of surgery in patients with metastatic bladder cancer.

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.

Defining the Cytokine Storm – DECYST 01

Background: Recent data have described a survival advantage associated with the administration of hyperthermic intra-peritoneal chemotherapy(HIPEC) following complete cytoreductive surgery(CRS) in ovarian cancer(OC). It is unlikely that HIPEC administered as a single dose has sufficient direct cytotoxicity to account for the improved survival. We hypothesise that HIPEC improves outcome by aborting a surgery induced cytokine storm, thereby reducing the proliferative stimulus to residual tumour cells.

Hyperthermic intraperitoneal chemotherapy (HIPEC) after primary debulking surgery in advanced epithelial ovarian cancer: Is BRCA mutational status making the difference?

IntroductionThe role of a molecular pattern predictive of hyperthermic intraperitoneal chemotherapy (HIPEC) efficacy in advanced ovarian cancer (AOC) patients has been poorly investigated. We aimed to assess the effect of HIPEC after primary debulking surgery (PDS) in AOC according to patient's Breast Cancer Gene (BRCA) mutational status. MethodsThis is a retrospective, single center, case-control study. Data on AOC patients receiving HIPEC at the end of PDS as previously enrolled in a phase II monocentric trial (HIPEC group), were retrieved and matched for clinical and surgical characteristics with a group of cases who underwent PDS without receiving HIPEC between 01/2010 and 01/2015 (No HIPEC group). Patients with International Federation of Gynecology and Obstetrics (FIGO) stage ≥IIIB disease, aged between 18 and 70 years, with a laparoscopic Predictive Index value (PIV) ≤8 and residual disease ≤2.5 mm were included. Results70 patients were included. With the except of age (p = 0.012), the populations were balanced for the main characteristics. At a median follow-up of 48 months, no differences in Progression Free Survival (PFS) (p = 0.968) and Overall Survival (OS) (p = 0.789) were recorded. Survival analysis according to HIPEC administration and BRCA mutational status showed an improved PFS (p = 0.011) and OS (p = 0.003) in BRCA mutated compared to wild-type patients when HIPEC was not administered, whilst they were superimposable in case of HIPEC administration (p = 0.857 vs p = 0.372; respectively). No differences in terms of neither intra-operative (p = 1.0) nor early post-operative complications (p = 0.920) were detected. ConclusionsOur results show that HIPEC in AOC may be a promising treatment in BRCA wild-type patients, as it seems to balance their decreased chemosensitivity compared to mutation carriers.

Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in the Management of Advanced Ovarian Cancer. A Literature Review

The rationale behind the use of hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery is the association between pharmacological activity of chemotherapy delivered to the peritoneal cavity with the enhanced cytotoxic effect of hyperthermia. Data on the efficacy of HIPEC in the primary debulking surgery (PDS) setting are still controversial and limited by the small sample size of most of the studies, the inclusion of different treatment settings and chemotherapy regimens. Among the ongoing prospective trials, only the OVHIPEC-2 trial is investigating exclusively patients submitted to PDS ± HIPEC with cisplatin 100 mg/m22 and results are expected by 2026. On the interval debulking surgery (IDS) setting high quality data are coming from the result of the OVHIPEC-1 trial, which demonstrated a survival advantage of nearly 4 months in median progression-free survival (PFS) (14.2 months vs. 10.7 months; p = 0.003) and almost 12 months in median overall survival (OS) (45.7 months vs. 33.9 months; p = 0.02) for HIPEC treated patients (cisplatin 100 mg/m22) compared to no-HIPEC group, with comparable morbidity. However, due to some criticisms raised to the results of OVHIPEC-1 trial, the ESMO-ESGO guidelines recommended not to consider HIPEC as standard therapy until results from ongoing randomized control trials (RCTs) are provided. On the contrary, for the National Comprehensive cancer network (NCCN) guidelines HIPEC can be considered at the time of IDS. Similarly, data supporting the role of HIPEC in association with surgery in case of recurrent disease appear to be controversial in terms of patients and selection and intraperitoneal chemotherapy regimen. Indeed, despite the positive results coming from a prospective randomized trial, they appear to be biased by the inclusion of both platinum sensitive and resistant disease and the lack of information on PFS. Those results are in contrast with data coming from another prospective trial, which failed to demonstrate a survival gain of recurrent ovarian cancer patients treated with secondary cytoreductive surgery + HIPEC with carboplatin (800 mg/m22 for 90 min) compared to women submitted to cytoreduction only. Again, in this subgroup of patients data of ongoing RCTs are awaited to assess the impact on survival of HIPEC administration in case of recurrent disease.

1839P Infectious complications post-cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: A meta-analysis

The intraoperative administration of Hyperthermic Intraperitoneal Chemotherapy is a novel treatment strategy that tries to provide similar therapeutic effects while avoiding some of the limitations of traditional treatment. The purpose of this analysis is to systemically review the available clinical studies to determine the infection rates postoperatively as complication of HIPEC with CRS procedure. As there are currently evolving guidelines for clinical application of this intervention this study helps in evaluating the safety of combined CRS and HIPEC for rates of infection.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: outcomes from a national centre in the current era.

Multimodal therapy incorporating cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) improve survival for selected patients with colorectal peritoneal metastases (CPMs). Many countries have centralised management of these patients, aiming to improve outcomes. There is ongoing debate on the need for and complications associated with HIPEC administration. We report indications and outcomes after CRS/HIPEC treated in a national centre in the modern era. A retrospective review of all CPM patients who underwent CRS and HIPEC since the initiation of an Irish national program in 2013. The primary endpoint was the overall survival associated with CRS/HIPEC. During the study period (April 2013-June 2020), 123 patients proceeded to planned CRS/HIPEC for CPM. Median age was 58 (IQR 47-67) and 55 patients (44.7%) were male. In 65 patients (52.8%), CPM was synchronous. In 7/123 (5.8%), disease was unresectable. The median peritoneal cancer index (PCI) was 10 (IQR 5-17). Overall, 104/123 (84.5%) underwent a complete cytoreduction (CC0/CC1). Thirteen out of 123 (10.5%) patients also had a synchronous liver resection. Forty out of 123 (32.5%) patients had adverse pathological features (poorly differentiated or signet ring cells). The median survival in patients after CC0, CC1 and CC2/3 resection was 50, 18 and 11months respectively (*p= < 0.0001, Log-rank Mantel-Cox). In total, 14/123(11.4%) had a major post-operative complication and 4/123 (3.3%) required re-operation. There was one (0.8%) post-operative death. The median length of stay was 14days (IQR 9-19). This study reports encouraging outcomes in patients with CPM undergoing CRS and HIPEC, especially when complete cytoreduction is achieved.

Pharmacokinetics and toxicity of carboplatin used for hyperthermic intraperitoneal chemotherapy (HIPEC) in treatment of epithelial ovarian cancer.

ObjectivesCarboplatin is frequently used in various doses for hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of epithelial ovarian cancer (EOC) although its pharmacokinetics, including focus on the perfusion time, has not been evaluated when used in modern era cytoreductive surgery (CRS). The aim was to evaluate the pharmacokinetics and hematological toxicity of carboplatin used for HIPEC with a perfusion time of 90 min.MethodsFifteen patients with stage III–IV primary EOC received CRS and 90 min of HIPEC with carboplatin at dose 800 mg/m2. For the pharmacokinetic analysis, perfusate and blood samples were obtained during HIPEC and up to 48 h after HIPEC (blood only). Hematological toxicity within 30 days was graded according to Common Terminology Criteria for Adverse Events. Severe toxicity (grades 3–5) is reported.ResultsMean maximum concentration of carboplatin was 12 times higher in perfusate than plasma (mean CmaxPF=348 µg/mL (range: 279–595 µg/mL) versus mean CmaxPL=29 µg/mL (range: 21–39 µg/mL)). Mean terminal half-life of carboplatin in perfusate was 104 min (range: 63–190 min) and mean intraperitoneal-to-plasma area under the concentration-time curve (AUC) ratio was 12.3 (range: 7.4–17.2). Two patients (13%) had grade 3 neutropenia within 30 days. No grade 4–5 hematological toxicities were identified.ConclusionsCarboplatin has a favorable pharmacokinetic profile for 90 min HIPEC administration, and the hematological toxicity was acceptable at dose 800 mg/m2. Large interindividual differences were found in the pharmacokinetic parameters, making risk of systemic exposure difficult to predict.

Incidence, predictors and clinical outcome of pancreatic fistula in patients receiving splenectomy for advanced or recurrent ovarian cancer: a large multicentric experience.

To evaluate the incidence, predictors and clinical outcome of pancreatic fistulas in patients receiving splenectomy during cytoreductive surgery for advanced or recurrent ovarian cancer. Data of women who underwent splenectomy during cytoreduction for advanced or recurrent ovarian cancer from December 2012 to May 2018 were retrospectively retrieved from the oncological databases of five institutions. Surgical, post-operative and follow-up data were analysed. Overall, 260 patients were included in the study. Pancreatic resection was performed in 45 (17.6%) women, 23 of whom received capsule resection alone, while 22 required tail resection. Hyperthermic intraperitoneal chemotherapy (HIPEC) was administered in 28 (10.8%) patients. In the overall population, a pancreatic fistula was detected in 32 (12.3%) patients, and pancreatic resection (p-value = 0.033) and HIPEC administration (p-value = 0.039) were associated with fistula development. In multivariate analysis, HIPEC (OR = 2.573; p-value = 0.058) was confirmed as a risk factor for fistula development in women receiving splenectomy alone, while concomitant cholecystectomy (OR = 2.680; p-value = 0.012) was identified as the only independent predictor of the occurrence of pancreatic fistulas in those receiving additional distal pancreatectomy. Although the median length of hospital stay was higher in women with pancreatic leakage (p-value = 0.008), the median time from surgery to adjuvant treatment was not significantly increased. HIPEC was identified as a risk factor for pancreatic fistulas in patients who underwent splenectomy alone, while concomitant cholecystectomy was the only independent predictor of fistula in those receiving additional pancreatectomy. The development of pancreatic leakage was not associated with increased post-operative mortality or delay in the initiation of chemotherapy.

RETRACTED ARTICLE: Upfront citorreduction and hyperthermic intraperitoneal chemotherapy with paclitaxel in patients with stage III-C serous epithelial ovarian cancer.

The main objective of this retrospective multicenter study, conducted by the Spanish Peritoneal Surgical Oncology Group (GECOP) was to analyze the survival outcomes of patients with stage IIIC serous epithelial ovarian cancer, after cytoreduction and intraoperative administration of hyperthermic intraperitoneal chemotherapy (HIPEC) with paclitaxel. Patients with stage IIIC serous epithelial ovarian cancer were recruited between May 2005 and October 2015, and treated by radical surgery using peritonectomy procedures, and HIPEC with paclitaxel. This multi-institutional retrospective study was carried out using a database containing prospectively collected parameters from five Spanish hospitals that were part of the GECOP. In total, 49 patients participated in the study. Complete cytoreduction (CC-0) was achieved in 38 patients (78%) and an optimal cytoreduction (CC-1) in the remaining 11 patients (22%). Following multivariate analysis, the presence of a Peritoneal Cancer Index (PCI) ≥ 20, and the impossibility of achieving a complete cytoreduction were independent factors associated with lower disease-free survival (DFS). The impossibility of achieving complete cytoreduction of disease, together with a PCI ≥ 14 were associated with an overall lower survival. Those patients with complete cytoreduction and who presented with a PCI < 14, reached a median DFS of 95months and an overall survival (OS) of 123months. HIPEC in patients with primary ovarian cancer is an alternative approach that requires serious evaluation for minimal residual disease treatment after complete cytoreduction.

Hyperthermic intraperitoneal chemotherapy in serosa-invasive gastric cancer patients

BackgroundEvaluation of hyperthermic intraperitoneal chemotherapy (HIPEC) in reducing metachronous peritoneal metastases (MPM) risks in patients with resectable serosa-invasive gastric cancer. Materials & methodsBetween 2008 and 2016, 154 patients with gastric cancer (stage IIB-IIIC) were randomly assigned to two groups: 76 patients underwent HIPEC (cisplatin 50 mg/m2 + doxorubicin 50 mg/m2, 42 °C, 1 h) combined with radical surgery (HIPEC group) and 78 patients underwent only radical surgery (control group). ResultsEvaluation of HIPEC toxicity showed neither toxic complications of IV-V degree nor haematological toxicity (according to CTCAE v. 4.03). There was no significant difference in the rate of complications between the two groups (p = 0.254). There was a more frequent disease progression in the control group than in the HIPEC group: 42/55 patients (76.4%) vs. 36/68 patients (52.9%), respectively (p = 0.009). At the same time a significant decrease in the rate of MPM was observed after HIPEC administration as compared with surgery alone – 16/68 (12.8%) vs. 39/55 (27.6%) (p < 0.001). 3-year progression-free survival was 47% (95% CI 36–61)) in the HIPEC group and 27% (95% CI 17–43) in the control group – p = 0.0024.The N-stage, HIPEC procedure, type of surgery and interaction between HIPEC treatment and age were independent prognostic factors. ConclusionsHIPEC appears to be helpful in improving treatment results in radically operated gastric cancer patients.

Laparoscopy in the diagnosis and treatment of peritoneal metastases

Over two decades the benefits of laparoscopy in the diagnosis and treatment of peritoneal metastases has been studied. Increasing utilization of this surgical tool has occurred with efficacy and safety demonstrated. The cancer surgery literature concerning the problem that peritoneal metastases presents, its adverse outcomes, and benefits of treatment were reviewed for patients with gastrointestinal malignancy. A major indication for laparoscopy is to determine the presence versus absence of peritoneal metastases. This may be especially important when planning treatments for gastric cancer. Repeated laparoscopy is used to monitor the efficacy of multiple cycles of intraperitoneal chemotherapy. Therapeutic laparoscopy involves the administration of hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with primary cancer who are at risk for subsequent peritoneal metastases or in those patients with peritoneal metastases diagnosed in follow-up. There are multiple applications of laparoscopy in patients with peritoneal metastases is indicated in many clinical situations as reviewed in this manuscript. Oftentimes, radiologic and laparoscopic assessments can be used to compliment each other.

Laparoscopy in the diagnosis and treatment of peritoneal metastases

Over two decades the benefits of laparoscopy in the diagnosis and treatment of peritoneal metastases has been studied. Increasing utilization of this surgical tool has occurred with efficacy and safety demonstrated. The cancer surgery literature concerning the problem that peritoneal metastases presents, its adverse outcomes, and benefits of treatment were reviewed for patients with gastrointestinal malignancy. A major indication for laparoscopy is to determine the presence versus absence of peritoneal metastases. This may be especially important when planning treatments for gastric cancer. Repeated laparoscopy is used to monitor the efficacy of multiple cycles of intraperitoneal chemotherapy. Therapeutic laparoscopy involves the administration of hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with primary cancer who are at risk for subsequent peritoneal metastases or in those patients with peritoneal metastases diagnosed in follow-up. There are multiple applications of laparoscopy in patients with peritoneal metastases is indicated in many clinical situations as reviewed in this manuscript. Oftentimes, radiologic and laparoscopic assessments can be used to compliment each other.

Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer

BackgroundTreatment of newly diagnosed advanced-stage ovarian cancer typically involves cytoreductive surgery and systemic chemotherapy. We conducted a trial to investigate whether the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery would improve outcomes among patients who were receiving neoadjuvant chemotherapy for stage III epithelial ovarian cancer.MethodsIn a multicenter, open-label, phase 3 trial, we randomly assigned 245 patients who had at least stable disease after three cycles of carboplatin (area under the curve of 5 to 6 mg per milliliter per minute) and paclitaxel (175 mg per square meter of body-surface area) to undergo interval cytoreductive surgery either with or without administration of HIPEC with cisplatin (100 mg per square meter). Randomization was performed at the time of surgery in cases in which surgery that would result in no visible disease (complete cytoreduction) or surgery after which one or more residual tumors measuring 10 mm or less in diameter remain (optimal cytoreduction) was deemed to be feasible. Three additional cycles of carboplatin and paclitaxel were administered postoperatively. The primary end point was recurrence-free survival. Overall survival and the side-effect profile were key secondary end points.ResultsIn the intention-to-treat analysis, events of disease recurrence or death occurred in 110 of the 123 patients (89%) who underwent cytoreductive surgery without HIPEC (surgery group) and in 99 of the 122 patients (81%) who underwent cytoreductive surgery with HIPEC (surgery-plus-HIPEC group) (hazard ratio for disease recurrence or death, 0.66; 95% confidence interval [CI], 0.50 to 0.87; P=0.003). The median recurrence-free survival was 10.7 months in the surgery group and 14.2 months in the surgery-plus-HIPEC group. At a median follow-up of 4.7 years, 76 patients (62%) in the surgery group and 61 patients (50%) in the surgery-plus-HIPEC group had died (hazard ratio, 0.67; 95% CI, 0.48 to 0.94; P=0.02). The median overall survival was 33.9 months in the surgery group and 45.7 months in the surgery-plus-HIPEC group. The percentage of patients who had adverse events of grade 3 or 4 was similar in the two groups (25% in the surgery group and 27% in the surgery-plus-HIPEC group, P=0.76).ConclusionsAmong patients with stage III epithelial ovarian cancer, the addition of HIPEC to interval cytoreductive surgery resulted in longer recurrence-free survival and overall survival than surgery alone and did not result in higher rates of side effects. (Funded by the Dutch Cancer Society; ClinicalTrials.gov number, NCT00426257; EudraCT number, 2006-003466-34.)