Addition Of Hyperthermic Intraperitoneal Chemotherapy Research Articles

Rationale and study design of the KOV-HIPEC-04: A phase III randomized controlled trial in primary stage III and IV ovarian cancer after interval cytoreductive surgery (FOCUS).

TPS5636 Background: The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) during interval cytoreductive surgery increases progression-free and overall survival for patients with stage III ovarian cancer in two randomized controlled trials (OV-HIPEC-01 and KOV-HIPEC-01) in the era of platinum. The aim of this trial is to identify the survival benefit of HIPEC in stage III & IV ovarian cancer with maintenance therapy of bevacizumab and/or PARP inhibitor. Methods: The KOV-HIPEC-04 trial is the international, multicenter, 1:1 randomized, phase III trial that will enroll 520 patients with stage III & IV ovarian cancer who received neoadjuvant chemotherapy. Patients with residual tumor < 2.5mm after interval cytoreductive surgery will be randomized to the trial arm (HIPEC, 41.0-42.0°C cisplatin 75mg/m2, 90 minutes) or control arm. After recovery from surgery, patients will receive postoperative platinum-based adjuvant chemotherapy followed by maintenance therapy with PARP inhibitor or bevacizumab by the institutional guideline based on BRCA/HRD status. The primary endpoint is to evaluate overall survival (OS); secondary objectives are progression-free survival (PFS), cancer-specific survival, time to the first subsequent therapy, safety, and quality of life. Assuming that the enrollment period is 5 years and the follow-up period is 3 years, the total number of events required is 263. Based on the log-rank test, the total number of subjects required to prove HR 0.67 with a two-sided alpha of 0.05 and 90% power is 494. Considering 5% drop-out, 520 patients are finally enrolled. ClinicalTrials.gov (NCT05827523). Clinical trial information: NCT05827523 .

Exploiting a subtype-specific mitochondrial vulnerability for successful treatment of colorectal peritoneal metastases

Peritoneal metastases (PMs) from colorectal cancer (CRC) respond poorly to treatment and are associated with unfavorable prognosis. For example, the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery in resectable patients shows limited benefit, and novel treatments are urgently needed. The majority of CRC-PMs represent the CMS4 molecular subtype of CRC, and here we queried the vulnerabilities of this subtype in pharmacogenomic databases to identify novel therapies. This reveals the copper ionophore elesclomol (ES) as highly effective against CRC-PMs. ES exhibits rapid cytotoxicity against CMS4 cells by targeting mitochondria. We find that a markedly reduced mitochondrial content in CMS4 cells explains their vulnerability to ES. ES demonstrates efficacy in preclinical models of PMs, including CRC-PMs and ovarian cancer organoids, mouse models, and a HIPEC rat model of PMs. The above proposes ES as a promising candidate for the local treatment of CRC-PMs, with broader implications for other PM-prone cancers.

Complexity of surgery and treatment burden in patients with peritoneal malignancy is not determined by addition of hyperthermic intraperitoneal chemotherapy.

This study describes surgical and quality of life outcomes in patients with peritoneal malignancy treated by cytoreductive surgery (CRS) alone compared with a subgroup treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC). Peritoneal malignancy patients undergoing surgery between 2017 and 2023 were included. The cohort was divided into patients treated by CRS and HIPEC and those treated by CRS without HIPEC (including CRS only or maximal tumour debulking (MTB)). Main outcomes included surgical outcomes, survival, and quality of life. Groups were compared using non-parametric tests and log-rank test was used to compare survival curves. 403 had CRS and HIPEC, 25 CRS only and 15 MTB. CRS and HIPEC patients had a lower peritoneal carcinomatosis index (12.0 vs. 17.0 vs. 35.0; P < 0.001) and longer surgical operative time (9.3 vs. 8.3 vs. 5.2 h; P < 0.001), when compared to CRS only and MTB, respectively. No other significant difference between groups was observed. The optimal management of selected patients with resectable peritoneal malignancy incorporates a combined strategy of CRS and HIPEC. When HIPEC is not utilized, due to significant residual disease or comorbidity precluding safe delivery, CRS alone is associated with good outcomes. Hospital stay and complications are acceptable but not significantly different to the CRS and HIPEC group. CRS alone is a complex intervention requiring comparable resources with good outcomes. In view of our findings 'intention to treat' with CRS and HIPEC should be the basis for resource allocation and funding.

Effect of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy on epithelial ovarian, fallopian tube, and peritoneal cancer: An institutional review of outcomes and its clinical implications

BACKGROUND: Ovarian, fallopian tube, and peritoneal cancer patients with advanced-stage diagnosis or recurrences spread to the peritoneal surface of the abdomen. Hyperthermic intraperitoneal chemotherapy (HIPEC) can penetrate and eradicate tumors that are microscopic up to those with a diameter of 2.5 cm from the peritoneal surface following cytoreductive surgery (CRS). OBJECTIVES: The study aimed to determine the efficacy and safety of CRS with HIPEC versus CRS alone for patients with epithelial ovarian, fallopian tube, and peritoneal cancer. MATERIALS AND METHODS: This retrospective cohort study included 50 patients (20 patients underwent CRS + HIPEC, while 30 patients underwent CRS alone). Records of these patients from January 2014 to June 2020 were reviewed, tabulated, and analyzed. RESULTS: The difference in recurrence rate between CRS with HIPEC and CRS alone was not statistically significant (50% vs. 43%, P = 0.774). The median time to recurrence was 10 and 9 months, respectively (P = 0.636). Five percent in the HIPEC group succumbed to the disease, while 13% died in the CRS alone group (P = 0.636). More post-operative complications were noted in the HIPEC group (45% vs. 10%, P = 0.007), but among these, only 2 cases had grade 3 to 4 complications (10%). The addition of HIPEC in the management of these patients resulted in a longer operative time (360 vs. 240 min, P &lt; 0.001) and postoperative hospital stay (8 vs. 6 days, P = 0.026). There were no intra- or peri-operative mortalities in both groups. CONCLUSION: CRS with HIPEC and CRS alone showed similar time to recurrence and recurrence rate. CRS with HIPEC had low risk of grade 3-4 complications and may still be considered as a treatment option for advanced, progressive, and recurrent epithelial ovarian, fallopian tube, and peritoneal cancer.

Interval Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy for Ovarian Cancer: Report of a Single-center Experience.

Emerging data suggest that addition of hyperthermic intraperitoneal chemotherapy (HIPEC) at the time of interval cytoreduction for patients with metastatic ovarian cancer is associated with a survival benefit. However, the implementation of this treatment is affected by concerns related to its potential morbidity. We present data from the first centre in the UK implementing HIPEC as part of treatment for patients with advanced ovarian cancer undergoing interval cytoreductive surgery. This is a prospective study of patients planned to undergo cytoreductive surgery and HIPEC for advanced ovarian cancer over a 30-month period. All patients had undergone neoadjuvant chemotherapy prior to surgery. Patients with stage III/IV ovarian cancer who underwent complete or near complete cytoreduction (<2.5 mm residual disease) received HIPEC using a closed technique. A total of 31 patients were included in the study, of which 30 had complete cytoreduction and 1 patient had residual disease <2.5 mm. The mean age of the patients was 63.7±2.8 years. Median peritoneal cancer index score was 9 (range=3-31). The mean operating time was 515.4±55.1 min. The mean length of hospital stay was 7.6±0.8 days. In total, 24 complications were observed in 18 patients (58.1%), while 6.5% of the patients experienced grade 3/4 complications. There were no deaths within 30-days from the surgery. Age was found to be an independent predictor of both postoperative complications of any grade and prolonged hospital stay. Interval cytoreductive surgery and HIPEC for patients with advanced ovarian cancer is associated with low perioperative morbidity.

Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy in patients with advanced ovarian cancer (OVHIPEC-1): final survival analysis of a randomised, controlled, phase 3 trial

The OVHIPEC-1 trial previously showed that the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery resulted in improved progression-free and overall survival compared with cytoreductive surgery alone at 4·7 years of follow-up in patients with stage III epithelial ovarian cancer who were ineligible for primary cytoreduction. We report the final survival outcomes after 10 years of follow-up. In this open-label, randomised, controlled, phase 3 trial, patients with primary epithelial stage III ovarian cancer were recruited at eight HIPEC centres in the Netherlands and Belgium. Patients were eligible if they were aged 18-76 years, had not progressed during at least three cycles of neoadjuvant carboplatin plus paclitaxel, had a WHO performance status score of 0-2, normal blood counts, and adequate renal function. Patients were randomly assigned (1:1) to undergo interval cytoreductive surgery without HIPEC (surgery group) or with HIPEC (100 mg/m2 cisplatin; surgery-plus-HIPEC group). Randomisation was done centrally by minimisation with a masked web-based allocation procedure at the time of surgery when residual disease smaller than 10 mm diameter was anticipated, and was stratified by institution, previous suboptimal cytoreductive surgery, and number of abdominal regions involved. The primary endpoint was progression-free survival and a secondary endpoint was overall survival, analysed in the intention-to-treat population (ie, all randomly assigned patients). This study is registered with ClinicalTrials.gov, NCT00426257, and is closed. Between April 1, 2007, and April 30, 2016, 245 patients were enrolled and followed up for a median of 10·1 years (95% CI 8·4-12·9) in the surgery group (n=123) and 10·4 years (95% CI 9·5-13·3) in the surgery-plus-HIPEC group (n=122). Recurrence, progression, or death occurred in 114 (93%) patients in the surgery group (median progression-free survival 10·7 months [95% CI 9·6-12·0]) and 109 (89%) patients in the surgery-plus-HIPEC group (14·3 months [12·0-18·5]; hazard ratio [HR] 0·63 [95% CI 0·48-0·83], stratified log-rank p=0·0008). Death occurred in 108 (88%) patients in the surgery group (median overall survival 33·3 months [95% CI 29·0-39·1]) and 100 (82%) patients in the surgery-plus-HIPEC group (44·9 months [95% CI 38·6-55·1]; HR 0·70 [95% CI 0·53-0·92], stratified log-rank p=0·011). These updated survival results confirm the long-term survival benefit of HIPEC in patients with primary stage III epithelial ovarian cancer undergoing interval cytoreductive surgery. Dutch Cancer Foundation (KWF Kankerbestrijding).

Final survival analysis of the phase III OVHIPEC-1 trial of hyperthermic intraperitoneal chemotherapy in ovarian cancer after ten year follow-up.

5509 Background: The randomized, phase 3 OVHIPEC-1 trial (NCT00426257) investigated the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery in patients with stage III epithelial ovarian cancer who were ineligible for primary cytoreduction. OVHIPEC-1 previously demonstrated improved recurrence-free and overall survival after 4.7 years of follow-up. Here, we report the final survival outcomes after ten years of follow-up. In addition, we report new data on the subsequent anti-cancer treatments given after disease progression. Methods: Patients were randomized to receive interval cytoreductive surgery with or without HIPEC, after receiving three cycles of neo-adjuvant carboplatin and paclitaxel. Randomization was performed at the time of surgery when either complete (no visible disease) or optimal cytoreduction (residual tumor measuring &lt;10mm in diameter) was anticipated. All patients received an additional three cycles of adjuvant systemic chemotherapy. We analyzed survival according to the intention-to-treat principle using stratified log-rank tests and Kaplan-Meier methods. Subsequent lines of therapy were compared between arms. Results: At a median follow-up of 10.1 years, 114 of 123 patients (92.7%) who underwent surgery alone and 109 of 122 patients (89.3%) who had surgery-plus-HIPEC experienced recurrence, progression, or death from any cause. Median recurrence-free survival was 10.7 months in the surgery group compared to 14.3 months in the surgery-plus-HIPEC group (HR, 0.63; 95% confidence interval [CI], 0.48-0.83; stratified P&lt;0.001). One hundred and eight patients (87.8%) in the surgery group have died as compared to 100 patients (82.0%) in the surgery-plus-HIPEC group. Median overall survival was 33.3 versus 44.9 months (HR, 0.70; 95% CI, 0.53-0.92; stratified P=0.011), respectively. Subsequent anti-cancer therapies, including chemotherapy (platinum and non-platinum based), secondary surgery, poly (ADP-ribose) polymerase (PARP) inhibitors and bevacizumab, were received by 104 patients (84.6%) in the surgery group and 100 patients (82.0%) in the surgery-plus-HIPEC group. The median number of subsequent systemic treatment lines was 2 (IQR 1-3) in both arms. Conclusions: This study provides the first long-term survival analysis of HIPEC in ovarian cancer and confirms the benefit of HIPEC in patients with primary stage III epithelial ovarian cancer undergoing interval cytoreductive surgery. No imbalance in subsequent therapy after disease recurrence was found that could explain the improved overall survival after HIPEC. Clinical trial information: NCT00426257 .

Pattern of Care in Real-World Scenario on Advanced Epithelial Ovarian Cancer in a Tertiary Referral Oncology Centre in India - ISPSM Collaborative Study.

The treatment of advanced epithelial ovarian cancer (EOC) has evolved over time. With advent of platinum-based chemotherapy and hyperthermic intraperitoneal chemotherapy (HIPEC), there is a paradigm shift in the patterns of care with improved survival. In this study, we analysed our advanced EOC patients aiming to gain insights into the pattern of care. An ambispective study of 250 patients of advanced EOC was done from our prospectively maintained computerised database in the Department of Surgical Oncology, tertiary care referral centre from 2013 to 2020. We analysed the demographic profile, treatment patterns, and perioperative outcomes. In this study, there were 83.6% stage III and 16.4% stage IVA. There were 62 (24.8%) upfront and 112 (44.8%) in interval settings. There was a higher number of patients receiving neo-adjuvant chemotherapy. One hundred twenty-six (50.4%) underwent cytoreductive surgery (CRS) only and 124 (49.6%) underwent CRS and HIPEC. CC-0 was achieved in 84.4% and CC-1 in 15.6% patients. HIPEC programme was started in 2013. With advent of RCTs in HIPEC, there was a substantial increase in the number of patients receiving HIPEC from 2015 (n = 10), 2017 (n = 20) to 2019 (n = 41). We offer secondary CRS in a limited subset of patients, n = 76 (30.4%). There was 24.8% early and 8.4% late postop complications. We have median follow-up of 50months with attrition rate of 4%. With practice changing updates, the treatment of advanced EOC has been evolving over time. Though the primary CRS followed by systemic therapy is the standard to date, there is change in pattern of care with neo-adjuvant chemotherapy followed by interval CRS and HIPEC because of various RCTs. The addition of HIPEC has acceptable morbidity and mortality. There is a definite learning curve and the team has to evolve as a whole. In a tertiary care referral centre from LMIC, good patient selection, logistics, and implementing recent advances will definitely add to improved survival.

Cost-effectiveness of hyperthermic intraperitoneal chemotherapy following interval cytoreductive surgery for stage III-IV ovarian cancer from a randomized controlled phase III trial in Korea (KOV-HIPEC-01)

BackgroundTo evaluate the cost-effectiveness of the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) following interval cytoreductive surgery (ICS) for stage III-IV ovarian cancer from a randomized controlled phase III trial. MethodsA comparative cost-effective analysis was performed using a Markov health-state transition model derived from the current trial cohort (ClinicalTrials.gov Identifier: NCT01091636). The incremental cost-effectiveness ratio (ICER) was evaluated by dividing the incremental costs by incremental quality-adjusted life-years (QALYs) with a time horizon of 10 years. Costs were calculated from the perspective of Korean healthcare, and health utility values were extracted from published sources. ResultsBased on data from the trial, the mean QALY in the ICS group was 7.16 compared to 10.8 in ICS followed by the HIPEC group. With an incremental QALY of 3.64, the ICS followed by HIPEC, was estimated to obtain an ICER of KRW 954,598 (USD 708.3) per QALY. ConclusionThe findings of the study suggest that ICS followed by HIPEC, is cost-effective with a significant gain in QALYs. These results may support the current reimbursement of HIPEC from Korean insurance services and the management of long-term conditions.

HIPEC after neoadjuvant chemotherapy is associated with acceptable toxicity and favorable quality of life in newly diagnosed advanced ovarian cancer patients (509)

HIPEC after neoadjuvant chemotherapy is associated with acceptable toxicity and favorable quality of life in newly diagnosed advanced ovarian cancer patients (509)

Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for small bowel neuroendocrine tumors with peritoneal metastasis

BackgroundUp to 20% of patients with small-bowel neuroendocrine tumors (SB-NETs) may present with peritoneal carcinomatosis (PM). Surgical cytoreduction (CRS) has been proposed as an adequate management as it confers a survival benefit in selected patients. The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to CRS in this context may be an option but data on its added benefits is lacking. MethodsA search was performed in the prospective multicenter international collaborative database of the Peritoneal Surface Oncology Group International (PSOGI) and BIG-RENAPE working groups, and patients who underwent a surgical treatment (CRS or CRS with HIPEC) for a SB-NET with PM were identified and compared. ResultsBetween 2002 and 2016, a total of 67 patients were identified as having a CRS for SB-NET, with 36 receiving HIPEC during surgery. Median postoperative follow-up was 34 months. The peritoneal cancer index (PCI) and the completeness of cytoreduction score (CCR-score) were higher in the CRS-HIPEC group. More grade III-IV complications occurred in this group as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0. Despite a tendency toward a better progression/recurrence-free survival in patients receiving HIPEC, no significant differences were noted between the CRS and CRS-HIPEC groups in terms of postoperative recurrence. ConclusionsHIPEC does not seem to provide additional benefits in terms of postoperative evolution and survival in patients with SB-NET undergoing CRS. It is associated with higher morbidity. It may possibly lead to an improved recurrence-free survival, but further reports are required to confirm this assumption.

The addition of sodium thiosulphate to hyperthermic intraperitoneal chemotherapy with cisplatin in ovarian cancer

Cisplatin based hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to prolong recurrence free and overall survival of women with ovarian cancer who have responded to neoadjuvant chemotherapy. The aim of this study was to assess the impact of cytoreductive surgery with or without the addition of HIPEC on renal function. MethodThis is a retrospective case-controlled study at a tertiary teaching hospital in Dublin, Ireland. All patients who had interval cytoreductive surgery (CRS) and HIPEC from October 2017 to October 2020 were included. A cohort of patients who had interval CRS without HIPEC were included as a control. Sodium thiosulphate (ST) was added to the HIPEC protocol in 2019. In order to assess the impact of ST as a renal protectant, renal function and post-operative outcomes were compared between the groups. ResultsSixty patients who had interval CRS were included, thirty of whom received cisplatin-based HIPEC. Seven received cisplatin 50 mg/m2 without the addition of ST. Twenty three patients received cisplatin 100 mg/m2 and ST. There were no statistically differences in age, body mass index BMI, American society of anaesthesia score, estimated blood loss or peritoneal cancer index between the cohorts (p > 0.05). The only episode of acute kidney injury (AKI) was within the HIPEC cohort, after cisplatin 50 mg/m2 (without ST) and this was sustained at three months. In contrast, no patients within the CRS cohort or cisplatin 100 mg/m2 that received the addition of ST, sustained a renal injury and all had a creatinine within the normal range at three days post operatively. ConclusionThe renal toxicity associated with cisplatin HIPEC and major abdominal surgery can be minimised with careful preoperative optimisation, intra operative fluid management and attention to renal function. The addition of sodium thiosulphate is a safe and effective method to minimise toxicity and should be added to any cisplatin HIPEC protocol.

Narrative review of hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with advanced ovarian cancer: a critical reappraisal of the current evidence.

The implementation of hyperthermic intraperitoneal chemotherapy (HIPEC) in the management of advanced stage epithelial ovarian cancer (EOC) as a standard practice remains debatable despite the emerging data supporting its beneficial effect when used to supplement cytoreductive procedures. The aim of the present review was an attempt to accumulate the currently available evidence on the use of HIPEC for patients with primary and recurrent EOC and to address directives of future research. Based on the currently available literature, the progress in cytoreductive surgical procedures and chemotherapy has brought significant improvement in the management and survival outcomes of selected patients with advanced EOC. The addition of HIPEC seems encouraging based on the outcomes of high-quality clinical trials. There are significant parameters on the use of CRS and HIPEC such as patient selection, the sequencing of procedures, the type of chemotherapy agent and time and the temperature of hyperthermic procedures which require additional investigation. Multidisciplinary team management by surgeons, gynaecologists, oncologists, pathologists and radiologists is of critical importance. Also, additional large prospective well-designed randomised studies are needed in order to update our current knowledge and provide guidelines to improve the management of patients with EOC.

Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis from Epithelial Ovarian Cancer: A 20-Year Single-Center Experience.

Simple SummaryMultimodality treatment is the standard treatment for epithelial ovarian cancer, but the peritoneum is the primary site of spread or relapse in most cases. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy has been introduced in order to improve outcomes, but most studies, including both primary and recurrent cases, are retrospective, non-randomized and heterogeneous. The aim of this study was to report a 20-year single-center experience with this treatment. In our study, it appeared to be a feasible procedure, with acceptable postoperative morbidity and mortality rates, providing different survival benefits depending on the timing of surgery, as long as a complete cytoreduction was obtained. Until the results from ongoing prospective randomized clinical trials clarify the role and appropriate indications, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy may be considered an effective treatment for selected cases of epithelial ovarian cancer, if performed in specialized centers.Despite improvement in treatments, the peritoneum remains the primary site of relapse in most ovarian cancer cases. Patients who underwent cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from epithelial ovarian cancer were reviewed. Kaplan–Meier curves and multivariate Cox analyses were used to identify survival rates and prognostic factors. This study included 158 patients. The procedure was mostly performed for recurrent disease (46.8%) and high-grade serous carcinoma (58.2%). The median peritoneal cancer index was 14, and complete cytoreduction was obtained in 87.9% of cases. Grade IV morbidity occurred in 15.2% of patients, mostly requiring surgical reoperation, and one patient (0.6%) died within 90 days. The median follow-up was 63.5 months. The Kaplan–Meier 5-year overall survival (OS) and disease-free survival (DFS) rates were 42.1% and 24.3%, respectively. Multiple regression logistic analyses demonstrated that the completeness of cytoreduction (CC) score (p ≤ 0.0001), pancreatic resection (p ≤ 0.0001) and number of resections (p = 0.001) were significant factors influencing OS; whereas the CC score (p ≤ 0.0001) and diaphragmatic procedures (p = 0.01) were significant for DFS. The addition of hyperthermic intraperitoneal chemotherapy to standard multimodality therapy may improve outcomes in both primary and recurrent epithelial ovarian cancer without impairing early postoperative results, but the exact timing has not yet been established. Prospective randomized studies will clarify the role and indications of this approach.

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

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

Outcome of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy +/- intraoperative radiation therapy in the management of peritoneal sarcomatosis: Real world experience.

e23581 Background: Sarcomas are aggressive malignancy,30-40% of them originate from retroperitoneal space. which makes adequate free surgical margin after surgical debulking mostly not achievable. The addition of Hyperthermic intraperitoneal chemotherapy (HIPEC)+/- Intraoperative radiation therapy (IORT) may overcome local failure with an overall survival benefit. we studied the outcome of cytoreductive surgery (CRS)+ HIPEC +/- IORT on patients with peritoneal sarcomatosis,at our institute. Methods: Patients with peritoneal sarcomatosis treated with CRS+ HIPEC +/- IORT, in the period between 2011-2016 were included. Results: 24 patients identified;15(62.5%) were males. Median age was 58(31-77). Liposarcoma was the most frequent diagnosis in 50% of them. Neoadjuvant chemotherapy was received in 5 patients, while neoadjuvant radiation therapy was received in 3 patients. Cytoreduction completeness score (CC-0/1) was achieved in 19(79.17%), with median peritoneal cancer index (PCI) of 11 (3–28). Melphalan was the most commonly used agent for HIPEC chemotherapy, it was used in 16(66.67%) patients. IORT was given in 16(66.67%) patients. 8 patients developed grade III-IV Clavien-Dindo (CD) complications, with one died 5 days post operatively due to pulmonary embolism. Adjuvant chemotherapy was received in 9 patients. After a median follow up of 21 months, the mean, 2 years and estimated 4 years progression free survival was 19.6 months, 30.6% and 15.3% respectively, 13(54.2%) patients developed systemic progression, lung was the most affected site at time of progression in 8/13(61.5%) patients. Local progression occurred in two patients, while both systemic and local progression occurred in one patient. The 3 cases progressed locally underwent redo CRS and HIPEC with average 18 months between the first and redo surgery. The mean, 2 years and estimated 4 years overall survival was 21.2 months, 75.7% and 75.7% respective. In univariate analysis only CC score correlate with PFS, the mean PFS for those patients with CC (0-1) vs (2-3) was 13.7 vs 11.5 months ( p = 0.036). Conclusions: Addition of HIPEC+IORT to surgical debulking in the management of peritoneal sarcomatosis; seems to be safe and may improve local control rate with a questionable survival benefit, a larger cohort with a multicentric study is needed for further evaluation.

Primary cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (HIPEC) for FIGO stage III epithelial ovarian cancer: OVHIPEC-2, a phase III randomized clinical trial

BackgroundThe addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery improves recurrence-free and overall survival in patients with FIGO stage III ovarian cancer who are ineligible for primary cytoreductive...

Hyperthermic intraperitoneal chemotherapy post cytoreductive surgery in management of peritoneal carcinomatosis of colorectal primaries: Tertiary center experience.

28 Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) in addition to Cytoreductive surgery (CRS) has survival benefit observed in management of Peritoneal Carcinomatosis (PC) from Colo-rectal cancer (CRC)origin. We report the outcomes and prognostic factors of patients with CRC, who presented with PC and underwent CRS and HIPEC at King Faisal Specialist Hospital &amp; Research Center, Riyadh, Saudi Arabia. Methods: Patients presented with PC from CRC origin and underwent CRS and HIPEC; from February 2009 to September 2015 were recruited. Results: 52 patients identified. A total of 55 CRS procedures were performed, where 3 patients underwent repeated CRS and HIPEC for tumor recurrence. All except 3 used mitomycin-C for HIPEC, the remaining received either melphalan (2 patients) or cisplatin plus mitomycin-C regimen (1 patient). Melphalan used for patients who underwent repeated HIPEC as 2nd line chemotherapeutic agent. Intraoperative Radiation therapy performed in 5 patients with tumor invading the surrounding structures, where performing a safe or complete resection was either technically difficult or carried high risk. Complication assessment by Clavien-Dindo score, 62 % grade (I-II), while 31% had grade (3–4). Two patients (3.6%) died postoperatively; both from sepsis. Respiratory complications were the most commonly encountered morbidities. The 5-year overall survival(OS) was 50% with disease free survival (DFS) 29.5%. Univariate analysis showed poor OS and DFS encountered in; Signet-ring tumors (p &lt; 0.0001) for both, peritoneal cancer index (PCI) ≥ 6 (p &lt; 0.0009) for both, completeness of cytoreduction(CC) score &gt;1 (p &lt; 0.0001) for both, and high 3-month postoperative carcinoembryonic antigen value (p &lt;0.0001) for both. In multivariate analysis; DFS was significant for (PCI) ≥ 6 (p &lt; 0.0131) and (CC) score &gt;1 (p &lt; 0.0031) while PCI &gt; 6 was the only significant factor (p &lt; 0.0030) for OS. Conclusions: Addition of HIPEC to CRS was safe, and improved survival in patient with peritoneal Carcinomatosis of colo-rectal origin. PCI and CC score are prognostic factors of survival, signet-ring subtype may not benefit of this procedure.

NCCN Guidelines Insights: Ovarian Cancer, Version 1.2019.

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years from diagnosis. A major challenge in treating ovarian cancer is that most patients have advanced disease at initial diagnosis. The best outcomes are observed in patients whose primary treatment includes complete resection of all visible disease plus combination platinum-based chemotherapy. Research efforts are focused on primary neoadjuvant treatments that may improve resectability, as well as systemic therapies providing improved long-term survival. These NCCN Guidelines Insights focus on recent updates to neoadjuvant chemotherapy recommendations, including the addition of hyperthermic intraperitoneal chemotherapy, and the role of PARP inhibitors and bevacizumab as maintenance therapy options in select patients who have completed primary chemotherapy.

Cost-effectiveness of hyperthermic intraperitoneal chemotherapy (HIPEC) at interval debulking of epithelial ovarian cancer following neoadjuvant chemotherapy

ObjectivesA recent randomized controlled trial demonstrated an overall survival benefit to the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to neoadjuvant chemotherapy (NACT) for stage III epithelial ovarian cancer (EOC). The objective of the current study was to quantify the cost-effectiveness of HIPEC in this setting. MethodsA decision analytic cost-effectiveness model was designed from a payer perspective to compare 2 surgical management strategies for EOC: (1) interval cytoreductive surgery (ICS); (2) ICS + HIPEC. Overall survival and ostomy rates with HIPEC were modeled from published studies. We assumed that 25% of each arm would later undergo secondary cytoreductive surgery, with the ICS arm eligible for HIPEC at that time. Costs were obtained from Medicare data, published studies, and the financial department of an academic hospital. Quality of life was not different between the arms; we assigned utilities based on a prior time-trade off study of ovarian cancer treatment. A Monte Carlo probabilistic sensitivity analysis was performed in the base case; primary outcome was the incremental cost-effectiveness ratio (ICER), expressed in 2017 US Dollars/quality-adjusted life years (QALYs). ResultsICS was the least costly strategy at $78,849, compared to ICS + HIPEC at $79,954. ICS + HIPEC was more effective than ICS (2.9 QALYs versus 2.45 QALYs for ICS). ICS + HIPEC was highly cost-effective, with an ICER of $2436/QALY compared to ICS. In one-way sensitivity analyses, probability of ostomy reversal and use of HIPEC at secondary cytoreduction did not substantially impact the cost-effectiveness of ICS + HIPEC. ConclusionICS + HIPEC constitutes cost-effective management of stage III EOC when NACT is performed.