Clinical Trial Protocol for HyNOVA: Hyperthermic and Normothermic intraperitoneal chemotherapy following interval cytoreductive surgery for stage III epithelial OVArian,fallopian tube and primary peritoneal cancer (ANZGOG1901/2020)

BackgroundOvarian cancer is the most lethal gynecological cancer, causing over 200,000 deaths worldwide in 2020. Initial standard treatment for primary ovarian cancer is optimal cytoreductive surgery (CRS) preceded and/or followed by intravenous platinum-based chemotherapy. However, most women develop recurrence within the peritoneal cavity and die of disease. Results of the OVIHIPEC 1 trial (2018) showed improved survival of 34% when hyperthermic intraperitoneal chemotherapy (HIPEC) was given immediately following interval-CRS in women with stage III disease. However, it is unknown if the effect of HIPEC is due to hyperthermia, one extra cycle of intraperitoneal (IP) chemotherapy, or other factors. There is also concern that hyperthermia might be associated with an increase in adverse events (AEs) due to a heightened systemic inflammatory response. HyNOVA is a seamless, multi-stage randomized study that attempts to answer these questions by comparing HIPEC to normothermic intraperitoneal chemotherapy (NIPEC), focusing on safety (stage 1), then assessing activity (stage 2) and effectiveness (stage 3). In this initial study, we hypothesize that NIPEC will result in a lower rate of severe AEs compared to HIPEC.MethodsThis initial stage of HyNOVA is a phase II study of 80 women with International Federation of Gynaecology and Obstetrics stage III epithelial ovarian cancer, with at least stable disease following 3–4 cycles of neoadjuvant chemotherapy, achieving interval-CRS to <2.5 mm residual disease. Participants are randomized 1:1 to receive IP cisplatin 100 mg/m² for 90 minutes either as HIPEC, heated to 42°C (41.5°C–42.5°C), or NIPEC, at 37°C (36.5°C–37.5°C). The primary outcome is the proportion of AEs ≥ grade 3 occurring within 90 days. Secondary outcomes are AE of interest, surgical morbidity, patient reported outcomes, resource allocation, feasibility, progression-free survival and overall survival. AEs are measured using both CTCAE v5.0 and Clavien-Dindo classification, particularly infection, pain, bowel dysfunction, and anemia. Tertiary outcomes are potential predictive biomarkers measured before and after HIPEC/NIPEC including circulating cell-free tumor DNA, tissue factors, and systemic inflammatory markers. There are 4 participating Australian sites with experience in CRS and HIPEC for peritoneal malignancy. HyNOVA is funded by an MRFF grant (APP1199155).Trial RegistrationANZCTR Identifier: ACTRN12621000269831p     

Intraperitoneal chemotherapy in the management of pancreatic adenocarcinoma: A systematic review and meta-analysis

BackgroundPancreatic cancer represents one of the leading causes of cancer-related death worldwide. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC), normothermic intraperitoneal chemotherapy (NIPEC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been proven with curative intent mainly for other tumors and there is a lack of consensus regarding possible benefits also in pancreatic cancer. The present systematic review and meta-analysis aim to provide an up-to-date overview of the effectiveness and safety of intraperitoneal treatments in the management of pancreatic cancer.MethodsA systematic review of articles was conducted according to PRISMA and AMSTAR-2 guidelines. 11 studies were included in the analysis.ResultsWe included in our analysis 212 patients subdivided in three groups: 64 in the HIPEC group (57 with prophylactic intent and 7 with curative intent), 55 in the PIPAC group and 93 in the NIPEC group. Primary outcomes were represented by survival rates; we evidenced at an observation time of three years a survival of 24% in the HIPEC group (25.5% in the prophylactic arm and 6.2% in the curative arm), 5.3% in the PIPAC group and 7.9% in the NIPEC group.ConclusionsHIPEC could be considered as a promising technique for prophylaxis and treatment of peritoneal metastasis (PM) in case of borderline resectable and locally advanced disease. Increased survival rates emerged without additional morbidity when surgical resection and CRS are possible. In addition, our data about PIPAC and NIPEC as palliative treatment in unresectable disease seems to identify more favorable survival rates compared to literature.     

Experimental study of antitumour activity and effects on leukocyte count of intraperitoneal administration and hyperthermic intraperitoneal chemoperfusion (HIPEC) with dioxadet in a rat model of ovarian cancer

Survival of rats with advanced ovarian cancer after intraperitoneal (i.p.) administration and hyperthermic intraperitoneal chemoperfusion (HIPEC) with dioxadet and effects of these treatment modalities on leukocyte count were evaluated in two independent series of experiments. Hyperthermic intraperitoneal chemoperfusion with dioxadet (15?mg/kg) provided median survival of rats of 49 days (95% CI 28–70), i.p. administration of dioxadet (1.5?mg/kg) of 28 days (95% CI 16–36; P?=?0.020). Single i.p. injection of dioxadet caused a significant decrease in total number of leukocytes (17–52%), granulocytes (18–75%), lymphocytes (18–62%) and monocytes (12–46%) in the peripheral blood of tumour-bearing rats compared to untreated animals. After HIPEC with dioxadet, the total number of leukocytes, granulocytes, lymphocytes and monocytes in peripheral blood of rats remained significantly higher than the corresponding values in the group with dioxadet.     

Antitumor activity of dioxadet compared with cisplatin on ascitic ovarian tumor in rats

Antitumor activity of dioxadet in comparison with cisplatin was studied on the model of ascitic ovarian tumor in 32 female Wistar rats. Ascitic ovarian tumor was transplanted intraperitoneally 0.5 ml per rat dissolved by saline in ratio 1 to 4. Dioxadet (1.5 mg/kg b.w.) and cisplatin (4.0 mg/kg b.w.) were administered intraperitoneally at their single maximal tolerable doses 48 hours after tumor cells transplantation. For drug activity estimation time to ascites detection and survival time values were used. In control group without no treatment the time till ascites occurrence and median life span were 5.4 +/- 0.25 and 7.5 days, correspondingly. In comparison with the control group dioxadet increased the average time of ascites occurrence and median of life span by 30% and 113% (p < 0.05), cisplatin increased these parameters by 28% and 147% (p < 0.05). Hence, antitumor activity of dioxadet is comparable with cisplatin activity for intraperitoneal therapy of the ascitic ovarian tumor.     

Usefulness of thermographic analysis to control temperature homogeneity in the development and implementation of a closed recirculating CO2 chemohyperthermia model

Purpose: To determine the effectiveness of thermography to control the distribution of abdominal temperature in the development of a closed chemohyperthermia model.

Materials and methods: For thermographic analysis, we divided the abdominopelvic cavity into nine regions according to a modification of carcinomatosis peritoneal index. A difference of 2.5?°C between and within the quadrants, and thermographic colours, were used as asymmetric criteria. Preclinical study:· Rats Model: Six athymic nude rats, male, rnu/rnu. They were treated with closed technique and open technique. Porcine Model: 12 female large white pigs. Four were treated with open technique and eight with closed recirculation CO₂ technique. Clinical Pilot Study, EUDRACT 2011-006319-69: 18 patients with ovarian cancer were treated with cytoreductive surgery and hyperthermia intraperitoneal chemotherapy, HIPEC, with a closed recirculating CO₂ system. Thermographic control and intra-abdominal temperature assessment was performed at the baseline, when outflow temperature reached 41?°C, and at 30´.

Results: The thermographic images showed a higher homogeneity of the intra-abdominal temperature in the closed model respect to the open technique. The thermogram showed a temperature distribution homogeneity when starting the circulation of chemotherapy. There was correlation between the temperature thermographic map in the closed porcine model and pilot study, and reached inflow and outflow temperatures, at half time of HIPEC, of 42/41.4?°C and 42?±?0.2/41?±?0.8?°C, respectively. There was no significant impact to the core temperature of patients after reaching the homogeneous temperature distribution.

Conclusions: To control homogeneity of temperature distribution is feasible using infra-red digital images in a closed HIPEC with CO₂ recirculation.     

Unusually favorable outcome of 6 consecutive patients with diffuse malignant peritoneal mesothelioma treated with repeated doses of intraperitoneal paclitaxel. A case series

BackgroundDiffuse malignant peritoneal mesothelioma (DMPM) is a disease in transition. Two decades ago this cancer had a median survival of 1 year. Recent reports in selected patients show a 5-year survival of 70% and median survival not reached at 10 years.MethodsConsecutive patients with a biopsy-confirmed diagnosis of DMPM, epithelial type, were treated by a consistent treatment plan. Cytoreductive surgery using peritonectomy procedures was always the first intervention. In the operating theater after all resections were complete but prior to intestinal reconstruction, hyperthermic intraperitoneal chemotherapy (HIPEC) using 2 cytotoxic agents was given. An intraperitoneal port was placed for normothermic intraperitoneal chemotherapy (NIPEC). Prospective data regarding pharmacokinetics, survival and adverse events were accumulated.ResultsSix consecutive patients were treated. Three to 6 one-week long cycles of normothermic intraperitoneal paclitaxel were administered through an intraperitoneal port. No systemic chemotherapy was given. Pharmacokinetic studies were performed on 5 patients. Four patients are free of disease at 8, 13, 18, and 19 years and two patients died of disease 15 years after definitive treatment. Three of 6 patients had a grade III/IV adverse event related to intraperitoneal chemotherapy administration through a port.ConclusionsThe small number of patients treated with repeated doses of intraperitoneal paclitaxel cause these data to be interpreted with caution. However, the long-term benefit and favorable pharmacology of these patients suggests the need for further study. Adverse events from this intraperitoneal port were recorded in half of the patients.     

Drugs,doses, and durations of intraperitoneal chemotherapy: standardising HIPEC and EPIC for colorectal,appendiceal, gastric,ovarian peritoneal surface malignancies and peritoneal mesothelioma

Abstract

Peritoneal surface malignancy (PSM) is a common manifestation of digestive and gynaecologic malignancies alike. At present, patients with isolated PSM are treated with a combination therapy of cytoreductive surgery (CRS) and hyperthermic peroperative intraperitoneal chemotherapy (HIPEC). The combination of CRS and intraperitoneal (IP) chemotherapy should now be considered standard of care for PSM from appendiceal epithelial cancers, colorectal cancer and peritoneal mesothelioma. Although there is a near universal standardisation regarding the CRS, we are still lacking a much-needed standardisation amongst the various IP chemotherapy treatment modalities used today in clinical practice. Pharmacologic evidence should be generated to answer important questions raised by the myriad of variables associated with IP chemotherapy.     

The effect of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) as an adjuvant in patients with resectable pancreatic cancer

Background – aims: The long-term survival of pancreatic cancer is poor even after potentially curative resection. The incidence of local-regional failures is high. There is evidence that hyperthermic intraperitoneal intraoperative chemotherapy (HIPEC) is effective in controlling the local-regional failures. The purpose of the study is to identify the effect of HIPEC after surgical removal of pancreatic carcinoma.

Patients – Methods: Prospective study including 33 patients with resectable pancreatic carcinomas. All patients underwent surgical resection (R₀) and ΗIPEC as an adjuvant. Morbidity and hospital mortality were recorded. The patients were followed-up for 5 years. Survival was calculated. Recurrences and the sites of failure were recorded.

Results: The mean age of the patients was 67.8?±?11.1 years (38–86). The hospital mortality was 6.1% (2 patients) and the morbidity 24.2% (8 patients). The overall 5-year survival was 24%. The mean and median survival was 33 and 13 months, respectively. The median follow-up time was 11 months. The recurrence rate was 60.6% (20 patients). Three patients were recorded with local-regional failures (9.1%) and the others with liver metastases.

Conclusions: It appears that HIPEC as an adjuvant following potentially curative resection (R₀) of pancreatic carcinoma may effectively control the local-regional disease. Prospective randomised studies are required.     

Hyperthermic chemotherapy intra-abdominal laparoscopic approach: development of a laparoscopic model using CO2 recirculation system and clinical translation in peritoneal carcinomatosis

Introduction: Hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective treatment for peritoneal carcinomatosis (PC). Laparoscopic surgery is performed in the treatment of colorectal and appendiceal cancer, and PC from diverse origin in selected patients. HIPEC management by laparoscopic approach after cytoreductive surgery (CRS) completed locoregional treatment of PC, and may be feasible and safe after appropriate patient selection.

Objective: Development of an experimental model of HIPEC by laparoscopic approach, with CO₂ recirculation. Clinical translation in two patients with PC and low peritoneal cancer index.

Material and methods: We performed CRS in a porcine model of 5 pigs (35–38?kg) by laparoscopic approach. Laparoscopic HIPEC by CO₂ recirculation system was performed; laparoscopic access was used for catheter input and output placement (Paclitaxel 175?mg/m² for 60?min at 42?°C). The experimental variables were: blood gases, haemodynamic and intra-abdominal and central temperature. Clinical model application was performed in three cases with PC from colorectal origin.

Results: No statistically significant differences was found in blood gases, haemodynamic or temperature in the experimental study. In clinical study, there were no technical complications during laparoscopic-HIPEC approach, and we observed no changes in haemodynamic variables during the procedure.

Conclusions: CRS and HIPEC laparoscopic model by CO₂ recirculation system is safe and feasible technique in selected patients, that include low PC index, local and accessible tumour recurrences or high-risk of PC tumours.     

Complete cytoreductive surgery plus HIPEC for peritoneal metastases from unusual cancer sites of origin: results from a worldwide analysis issue of the Peritoneal Surface Oncology Group International (PSOGI)

Abstract

Aim: The aim of this study was to assess the outcomes of patients operated on for peritoneal metastases from unusual cancer sites of origin, meaning apart from peritoneal metastases (PM) from colorectal, gastric and epithelial ovarian carcinomas, pseudomyxoma peritonei and mesothelioma.

Patients and methods: A questionnaire concerning patients treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for PM arising from unusual cancer sites of origin was sent to all centres, which routinely performed HIPEC, through the Peritoneal Surface Oncology Group International and the RENAPE network.

Results: Between September 1990 and June 2016, 850 procedures for unusual cases were performed in 781 patients, in 53 centres worldwide. Nearly two-thirds of the procedures were performed for three indications: rare ovarian carcinoma (n?=?224), sarcoma (n?=?189) and neuroendocrine tumours (n?=?127). The median PCI was 12 [0–39]. Grade III–IV postoperative complications occurred in 272 patients (41%). Nineteen patients (2.9%) died postoperatively. After a median follow-up of 46?months, median overall survival (OS) was 39?months [33.18–44.05]. Five-year OS rate was 38.7%. For the three main indications, 5-year OS was significantly greater in patients with PM from rare ovarian carcinoma (57.7%), than that of patients with PM from neuroendocrine tumours (39.9%), and from sarcoma (29.3%) (p?<?0.0001).

Conclusions: CRS and HIPEC appear to be safe and effective in patients with peritoneal metastases from unusual cancer sites of origin, especially from rare ovarian carcinomas, PM from neuroendocrine tumours. The respective roles of CRS and HIPEC remain unclear and should be evaluated.     

Intraperitoneal chemotherapy hyperthermia (HIPEC) for peritoneal carcinomatosis of ovarian cancer origin by fluid and CO2 recirculation using the closed abdomen technique (PRS-1.0 Combat): A clinical pilot study

Background This paper reports a study of 21 patients with peritoneal carcinomatosis from ovarian cancer who underwent cytoreductive surgery and HIPEC by means of PRS-1.0 Combat®, a new model for closed abdomen HIPEC aimed at improving fluid distribution with assistance from a CO₂ recirculation system. This new technology has been previously shown to be successful in an experimental study (pig model) performed by our group, and has been approved for use in our hospital. Methods Twenty-one patients with peritoneal carcinomatosis of ovarian cancer origin were included in the study. Cytoreductive surgery and HIPEC were performed by a closed abdomen fluid and CO₂ recirculation technique using the PRS-1.0 Combat^® model. We analysed the intraoperative safety tolerance and post-operative morbidity and mortality during the first 30 days. Results Between November 2011 and March 2014 21 patients with epithelial ovarian cancer, International Federation of Gynecology and Obstetrics stage II–IV, were included in the study. During the procedure there were no significant haemodynamic or analytical disturbances. Complication rates were 38.1% and 57.14% for grade III/IV and minor (grade I/II) complications, respectively. Post-operative mortality was 4.76% (one patient). Complete cytoreductive surgery and intraperitoneal chemotherapy improved overall survival and disease-free survival in women with advanced ovarian cancer. The association of intra-abdominal hyperthermia with chemotherapy (HIPEC) increased the therapeutic benefit. Conclusions This study has shown that closed abdomen intraperitoneal chemohyperthermia by a fluid and CO₂ recirculation system (PRS-1.0 Combat^®) can be a safe and feasible model for the treatment of peritoneal carcinomatosis of ovarian cancer origin.     

After thirty years of experience with early postoperative intraperitoneal 5-fluorouracil now saying goodbye

In the management of colorectal and appendiceal peritoneal metastases, intraperitoneal 5-fluorouracil (5-FU) has been used in 3 different ways. It has been used as part of an early postoperative intraperitoneal chemotherapy (EPIC) regimen along with EPIC mitomycin C. This EPIC mitomycin C plus EPIC 5-FU has been shown to be equivalent or inferior to HIPEC. Because it is more work intensive than HIPEC and not superior, its use should be abandoned if HIPEC is available. A second way to use intraperitoneal 5-FU is along with HIPEC. Several studies suggest a survival advantage for the combination of HIPEC with EPIC 5-FU. However, patient ineligibility for EPIC 5-FU in high-risk CRS is more likely the cause for the alleged survival advantage attributed to the combination. A third use of intraperitoneal 5-FU is long-term through a peritoneal access device. This plan for 5-FU use has shown favorable results in three randomized controlled studies. Normothermic intraperitoneal chemotherapy (NIPEC) with 5-FU should be considered as a regional chemotherapy component of a randomized trial for prevention or treatment of peritoneal metastases from colorectal or appendiceal cancer. Intravenous oxaliplatin combined with NIPEC 5-FU has been suggested as a bidirectional adjuvant regimen.     

Current status and future prospects of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) clinical trials in ovarian cancer

Abstract

The natural history of advanced-stage epithelial ovarian cancer is one of clinical remission after surgery and platinum/taxane-based intravenous (IV) and/or intraperitoneal (IP) chemotherapy followed by early or late recurrence in the majority of patients. Prevention of progression and recurrence remains a major hurdle in the management of ovarian cancer. Recently, many investigators have evaluated the use of normothermic and hyperthermic intraoperative IP drug delivery as a management strategy. This is a narrative review of the current status of clinical trials of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) in ovarian cancer and the future directions for this treatment strategy. The existing studies on HIPEC in patients with epithelial ovarian cancer are mostly retrospective in nature, are heterogeneous with regards to combined inclusion of primary and recurrent disease and lack unbiased data. Until data are available from evidence-based trials, it is reasonable to conclude that surgical cytoreduction and HIPEC is a rational and interesting, though still investigative, approach in the management of epithelial ovarian cancer, whose use should be employed within prospective clinical trials.     

Intra-abdominal temperature distribution during consolidation hyperthermic intraperitoneal chemotherapy with carboplatin in the treatment of advanced stage ovarian carcinoma

Abstract

Purpose: Hyperthermic intraperitoneal chemotherapy (HIPEC) involves the continuous heating and circulation of chemotherapy throughout the abdominal cavity in an attempt to enhance cytotoxicity. Despite the potential of this chemotherapy procedure, there are scant anatomical temperature distribution studies reporting on this therapeutic process. Patients and methods: We prospectively evaluated the temperature of select anatomical (e.g. upper abdominal, mid-abdominal and supra-pubic) sites in 11 advanced stage ovarian cancer patients who were treated with consolidation HIPEC carboplatin (AUC 10). The temperature of the aforementioned anatomical regions and the inflow/outflow tubing was measured at baseline and at 15-min intervals until the procedure’s completion. Results: The lowest observed mean composite temperature was 41.1?°C at the supra-pubic site whereas the highest temperature was 42.6?°C, in association with the inflow/outflow tubing. During the various time intervals we also ascertained that the lowest composite temperature was 40.9?°C at baseline (i.e. time 0), whereas the highest value (41.8?°C) occurred at multiple time periods (e.g. 15, 45 and 60?min). Conclusion: The HIPEC temperature variation amongst the various abdominal sites and time intervals was minimal. We also discerned that uniform temperature distribution throughout the abdominal cavity was facilitated when the abdomen was both maximally distended with fluid and a high flow rate was maintained.     

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal malignancy: preliminary results of a multi-disciplinary teamwork model in Asia

Background: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is an emerging surgical procedure for peritoneal carcinomatosis (PC). CRS/HIPEC is a complicated treatment that requires multi-disciplinary teamwork (MDT), which may be lacking when establishing a CRS/HIPEC programme. Herein, we report our preliminary treatment outcomes with the early implementation of an MDT model for CRS/HIPEC.

Methods: From April 2015 to December 2016, 45 patients with a diagnosis of PC who received CRS/HIPEC were reviewed retrospectively in a single institution in Taiwan.

Results: Among the 45 patients, CRS was mainly performed by laparotomy (n?=?42), and only three patients with limited PC underwent laparoscopic CRS. The first 13 patients received treatment before the MDT had been established (group 1), and the other 32 patients were treated after the MDT had been established (group 2). The highest peri-HIPEC body temperature in group 2 was significantly lower than that in group 1 (36.8?°C vs. 37.5?°C, p?p?=?0.202). Pre-CRS/HIPEC abdominal pain significantly increased the risk of post-operative major complications (p?=?0.017).

Conclusions: Our experience suggests that the early implementation of an MDT model when establishing a CRS/HIPEC programme at a single institution may result in a higher complete cytoreduction rate and lower major complication rate, and also shorten the learning curve of this complicated procedure.     

Clinical efficacy of cytoreductive surgery and hyperthermic chemotherapy in peritoneal carcinomatosis from gastric cancer

Evaluation of: Yang XJ, Huang CQ, Suo T et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a Phase III randomized clinical trial. Ann. Surg. Oncol. 18(6), 1575–15781 (2011).

Peritoneal carcinomatosis (PC) is the most common pattern of metastasis and recurrence in patients with gastric cancer and is associated with poor clinical outcome and survival. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) was recently established as a new treatment option for PC of gastrointestinal cancer. However, the role of cytoreductive surgery in gastric cancer and the intrinsic role of HIPEC remains unclear. The evaluated article presented a single center Phase III study, randomizing 68 patients with PC from gastric cancer to surgical cytoreduction only (CRS; n = 34) versus cytoreduction plus HIPEC with cisplatin and mitomycin (CRS+HIPEC; n = 34). Median overall was 6.5 months in the CRS group and 11.0 months in the CRS+HIPEC group (p = 0.046). Serious adverse events were acceptable in both groups. Multivariate analysis found CRS+HIPEC, synchronous PC, complete cytoreduction, systemic chemotherapy >6 cycles and no incidence of severe adverse events independent predictive factors for survival. This was the first study to show the positive effects of HIPEC in addition to CRS in PC independently of the tumor entity. In patients with gastric cancer, multimodal treatment concepts combining surgical cytoreduction and HIPEC may provide a new option in carefully selected patients.     

Intraperitoneal chemotherapy against peritoneal carcinomatosis: Current status and future perspective

Peritoneal carcinomatosis (PC), caused by advanced abdominal malignancies, such as those of the ovarian and gastrointestinal tracts, has an extremely poor prognosis. Intraperitoneal (IP) chemotherapy has been clinically applied for several decades, but its clinical efficacy has not been fully determined. An accumulating body of evidence suggests that cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is the optimal treatment for selected patients with ovarian and colorectal cancers with PC. Recent studies suggest that IP administration of taxane with systemic chemotherapy in a neoadjuvant setting improves patient survival in gastric cancer with PC. The pharmacokinetics of IP-administered drugs should be primarily considered in order to optimize IP chemotherapy. Therefore, the development of specific IP drugs using newly emerging molecular targeted reagents or new drug delivery systems, such as nanomedicine or controlled absorption/release methods, is essential to improve the efficacy of IP chemotherapy.     

Residual tumour less than 0.25 centimetres and positive lymph nodes are risk factors for early relapse in recurrent ovarian peritoneal carcinomatosis treated with cytoreductive surgery,HIPEC and systemic chemotherapy

Aim: The cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has showed promising results for the survival in patients with recurrent ovarian carcinomatosis, however, some of them will recur within the first year. The aim of this study is focussed on identifying the risk factors to develop the recurrence within the first year after an optimal CRS-HIPEC in patients with recurrent ovarian carcinomatosis.

Methods: A total of 100 patients with peritoneal carcinomatosis from recurrent ovarian cancer treated by CRS?+?HIPEC were selected for analysis. Multivariate logistic regression analysis was performed to evaluate the relationship between the variables and the early recurrence.

Results: The mean follow-up was 42.5 months. The mean age was 56.2 years. Early recurrence was observed in the 36%. The group early recurrence presented a higher rate of optimal cytoreductions CC1 (16.2% vs. 3.5%), lymph nodes (32.5% vs. 15%) and the use of hemoderivates (40.5% vs. 33%). Others parameters as Peritoneal Cancer Index, major morbidity? 3, re-operations rate and time to adjuvant chemotherapy were similar in both groups. The five years OS was 58%, for the non-early recurrence was higher than the early recurrence group (64% vs. 41%). In the multivariate analysis, CC-1 (OR 5.73; 1.16–32.04) and positive lymph nodes (OR 2.26; 1.01–4.32) proved to be independent factors for the early recurrence.

Conclusion: The combination of both (CC1 and positive lymph nodes) makes that the indication of CRS and HIPEC should be individualised. However, the major morbidity, stage IV and the time to the adjuvant treatment were not associated with an early recurrence, so that, a major aggressiveness is recommended to achieve a CC0.     

Platinum agents and mitomycin C-specific complications in cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)

Introduction: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been found to prolong survival in patients with peritoneal disease but is associated with significant morbidity. We evaluate the perioperative complications and the association with the chemotherapy agent used for HIPEC.

Methods: Retrospective analysis of a prospectively collected database of CRS–HIPEC cases between April 2001 and February 2016 was performed. Patients were stratified by the chemotherapy used, and perioperative complications were compared.

Results: Out of 214 CRS–HIPEC cases, 113 procedures used Mitomycin-C(MMC), 92 used cisplatin, 8 used oxaliplatin and the HIPEC regimen for one procedure was not recorded and excluded. 94 patients (44%) suffered low-grade complications (grade I–II), and 49 patients (23%) suffered high-grade complications (grade III–V). The frequency of low-grade complications for the cisplain, oxaliplatin and MMC groups were 49%, 50% and 40%, respectively, whereas that of high-grade complications were 24%, 50% and 20%, respectively. HIPEC with platinum agents was associated with a higher rate of acute renal impairment (ARI) compared to MMC (32% and 62% for cisplatin and oxaliplatin vs. 5.6% for MMC), whereas grade IV ARI requiring dialysis occurred only in the cisplatin group (5.6%). HIPEC with oxaliplatin was associated with higher rates of post-operative bleeding (25% vs. 1.1% and 0.88%). Rates of other complications did not differ significantly between the groups receiving different HIPEC regimens.

Conclusions: The overall complication rates do not significantly differ after HIPEC with MMC and platinum based agents. Renal impairment tends to be more common and of greater severity when a platinum agent is used, whereas oxaliplatin is associated with significant post-operative bleeding.