Understanding nutrition challenges and information needs of women undergoing cytoreductive surgery for ovarian cancer: a study protocol for an experience-based co-design methodology

The Fifth Annual Advanced Course in Cytoreductive Surgery for Ovarian Cancer and Peritoneal Surface Malignancies was held at and sponsored by the Division of Gynecologic Oncology at the the University of California, Irvine on Friday and Saturday, October 9-10, 2015. The workshop was comprised of didactic modules, historical treatise, an impassioned tribute, a cadaver laboratory, and heated intraperitoneal chemotherapy demonstration. This was a not-for-profit workshop, and registration fees were used to support course faculty travel to U.C. Irvine and to pay for the cadavers. The original 56 available spots were filled within three weeks of the initial announcement, prompting procurement of two additional cadavers to satisfy registration overflow and accommodate the six U.C. Irvine fellows-in-training. While international participation in the Workshops continues to rise, we have also noted more U.S.-trained Gynecologic Oncologists among the registrants.

Hyperthermic intraperitoneal chemotherapy for recurrent ovarian cancer (CHIPOR): a randomised, open-label, phase 3 trial

e16476 Background: Peritoneal surface malignancies (PSM) are highly aggressive cancers with limited treatment access in low- and middle-income countries (LMICs). Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has redefined survival outcomes globally, yet its feasibility and impact in LMICs remain underexplored. This first multicenter study in North Africa aimed to evaluate the efficacy and implementation of CRS with or without HIPEC, providing a critical benchmark for global oncology care in resource-limited settings. Methods: This retrospective cohort study included patients with histologically confirmed PSM (arising from colorectal cancer, pseudomyxoma peritonei, ovarian cancer, gastric cancer, or mesothelioma) treated with complete CRS with or without HIPEC between January 2014 and December 2020 at three tertiary centers in Rabat (Morocco), Tunis (Tunisia), and Batna (Algeria). The study protocol, including treatment protocols and endpoints—overall survival (OS), disease-free survival (DFS), and severe postoperative morbidity (Clavien-Dindo grade ≥ IIIa)—was reviewed prior to implementation. Multivariate Cox regression was used to identify independent predictors of survival outcomes. Results: A total of 391 patients were included in the study, with colorectal cancer (43%), pseudomyxoma peritonei (36%), ovarian cancer (12%), gastric cancer (6%), and mesothelioma (2%) as the primary tumor types. Complete cytoreduction (CC-0/1) was achieved in 88% of cases, and HIPEC was performed in 39%. Severe morbidity occurred in 22% of cases, with spleno-pancreatectomy, incomplete cytoreduction, and HIPEC identified as significant predictors. Mortality was reported in 6% of cases. The median overall survival (OS) was 68 months, with 1- and 5-year survival rates of 97% and 56%, respectively. The median disease-free survival (DFS) was 48 months. Patients undergoing CRS with HIPEC had significantly longer OS compared to those receiving CRS alone (70 months vs. 64 months, p = 0.016). No significant difference in DFS was observed between the two groups. Independent predictors of improved OS included primary tumor type, PCI, CC score, and HIPEC. For DFS, older age and lower tumor burden were protective factors, while incomplete cytoreduction was associated with worse outcomes. Conclusions: This pioneering study establishes that CRS and HIPEC are feasible and effective in LMICs, achieving survival outcomes comparable to high-income settings. With a median OS of 68 months and significant improvements in long-term survival, we highlight the potential for CRS and HIPEC to deliver meaningful disease control and long-term survival, even in resource-constrained settings. These results set a foundation for scaling advanced PSM treatments in LMICs, setting a new standard for global oncology care.

Introduction: The role of surgery for peritoneal carcinomatosis (PC) has slowly evolved from palliation to potential curative intent. Attempting to remove all visible tumor deposits, “surgical cytoreduction” (CRS) was reported in 1930s for ovarian cancer and eventually became an accepted therapy with proven survival benefit. The new approach of combining CRS and hyperthermic intraperitoneal chemotherapy (HIPEC) to treat peritoneal metastasis offer hope for long term survival in this group of patients. The risk and benefit of this approach continued to be debated. A prospective study was conducted to understand the perioperative outcomes of CRS and HIPEC. Aim: To evaluate the perioperative outcomes associated with CRS and HIPEC in Advanced and Recurrent Epithelial Ovarian Cancer with PC. Method: Prospective analysis of patients undergoing CRS and HIPEC from November 2014 to July 2015 was done. Inclusion criteria included localized disease in peritoneal cavity, no distant metastasis and PS <2. Grade 3/4 complications from day of surgery until 30 days postoperatively were recorded. Results: We performed CRS and HIPEC in 20 patients from November 2014 to June 2015. HIPEC Plus regimens included Cisplatin (50 mg/m2) and Lipodox (15 mg/m2) intraperitoneally and Ifosphamide (1300 mg/m2) and Mesna (260 mg/m2). Infusion time was 90 minutes with a temperature range of 41-43°C. Out of 20 patients 6 (30%) underwent primary debulking surgery and 14 (70%) underwent secondary debulking surgery. PCI score ranged from 2-26 (mean 13.65). Mean operating time was 6.42 hrs and average blood loss was 1046 ml. Average hospital stay was 8 days and SICU stay was 4.9 days (range 3-14 days). Total 26 adverse events were observed of which grade 1 were 11 (42%), grade 2 were 8 (30%), grade were 3 (11.5%) and grade 4 were 2 (8%). Most common complication was hematological (8) followed by respiratory (6), sepsis (4) renal (2), GI (2). 4 patients (5 events) developed grade 3 or 4 complications in the form of septicaemia, pulmonary embolism, GI fistula of which 2 patients expited and remaining recovered although required prolonged hospitalization. Increased morbidity were observed in cases with symptomatic relapse, higher PCI score and CA 125 level higher than 250 U/ml. Most of the adverse events were grade 1 and 2 and were managed by observation only or GCSF support, transfusions and other minor interventions. The combined grade 3-4 morbidity was 20% (4 out of 20) which consisted of neutropenia, infection and respiratory complications. One patient required relaparotomy and two patients expired attributed to pulmonary embolism and septicaemia respectively. Conclusion: Enthusiasm associated with improvement in survival is often dampened by increased perioperative mortality and morbidity figures and therefore CRS and HIPEC has not yet been considered standard of care by many centres. HIPEC after extensive cytoreductive surgery for ovarian cancer is a procedure whth acceptable morbidity that patients can tolerate. More follow up is needed to determinr the effect of HIPEC on survival. Till such time more data are obtained by way of larger randomised trials, this approach remains investigational.

Introduction: The role of surgery for Peritoneal carcinomatosis (PC) has slowly evolved from palliation to potential curative intent. Attempting to remove all visible tumor deposits, “surgical cytoreduction” (CRS) was reported in 1930s for ovarian cancer and eventually became an accepted therapy with proven survival benefit. The new approach of combining CRS and Hyperthermic intraperitoneal chemotherapy (HIPEC) to treat peritoneal metastasis offer hope for long term survival in this group of patients. The risk and benefit of this approach continued to be debated. A prospective study was conducted to understand the perioperative outcomes of CRS & HIPEC. Aim: To evaluate the perioperative outcomes associated with CRS & HIPEC in Advanced and Recurrent Epithelial Ovarian Cancer with PC. Methods: Prospective analysis of patients undergoing CRS & HIPEC from November 2014 to July 2015 was done. Inclusion criteria included localized disease in peritoneal cavity, no distant metastasis and PS <2. Grade 3/4 complications from day of surgery until 30 days postoperatively were recorded. Results: We performed CRS & HIPEC in 20 patients from Nov 2014 to June 2015. HIPEC Plus regimens included Cisplatin (50 mg/m2) and Lipodox (15 mg/m2) intraperitoneally and Ifosphamide (1300 mg/m2) & Mesna (260 mg/m2) Infusion time was 90 minutes with a temperature range of 41-43 °C. Out of 20 patients 6 (30%) underwent primary debulking surgery and 14(70%) underwent secondary debulking surgery. PCI score ranged from 2-26 (mean 13.65). Mean operating time was 6.42 hrs and average blood loss was 1046 ml. Average hospital stay was 8 days and SICU stay was 4.9 days (range 3-14 days). Total 26 adverse events were observed of which grade 1 were 11 (42%), grade 2 were 8 (30%), grade were 3 (11.5%) and grade4 were 2 (8%). Most common complication was hematological (8) followed by respiratory (6), sepsis (4) renal (2), GI (2). 4 patients (5 events) developed grade3 or 4 complications in the form of septicaemia, pulmonary embolism, GI fistula of which 2 patients expited and remaining recovered although required prolonged hospitalization. Increased morbidity were observed in cases with symptomatic relapse, higher PCI score and CA 125 level higher than 250 U/ml. Most of the adverse events were grade 1 and 2 and were managed by observation only or GCSF support, transfusions and other minor interventions. The combined grade 3-4 morbidity was 20% (4out of 20) which consisted of neutropenia, infection and respiratory complications. One patient required relaparotomy and two patients expired attributed to pulmonary embolism and septicaemia respectively. Conclusion: Enthusiasm associated with improvement in survival is often dampened by increased perioperative mortality and morbidity figures and therefore CRS & HIPEC has not yet been considered standard of care by many centres. HIPEC after extensive cytoreductive surgery for ovarian cancer is a procedure whth acceptable morbidity that patients can tolerate. More follow up is needed to determinr the effect of HIPEC on survival. Till such time more data are obtained by way of larger randomised trials, this approach remains investigational.

Objectives: To assess the individual treatment strategies among international experts in peritoneal carcinosis, specifically their decision-making in the process of patient selection for hyperthermic intraperitoneal chemotherapy (HIPEC) in women suffering from ovarian cancer, to identify relevant decision-making criteria, and to quantify the level of consensus for or against HIPEC. Methods: The members of the executive committee of the Peritoneal Surface Oncology Group International (PSOGI) were asked to describe the clinical conditions under which they would recommend HIPEC in patients with ovarian cancer and to describe any disease or patient characteristics relevant to their decision. All answers were then merged and converted into decision trees. The decision trees were then analyzed by applying the objective consensus methodology. Results: Nine experts in surgical oncology provided information on their multidisciplinary treatment strategy including HIPEC for patients with advanced ovarian cancer. Three of the total of 12 experts did not perform HIPEC. Five criteria relevant to the decision on whether HIPEC is performed were applied. In patients with resectable disease, a peritoneal cancer index (PCI) <21, and epithelial ovarian cancer without distant metastasis, consent was received by 75% to perform HIPEC for women suffering from recurrent disease. Furthermore, in the primary disease setting, consent was received by 67% to perform HIPEC according to the same criteria. Discussion and Conclusion: Among surgical oncology experts in peritoneal surface malignancy and HIPEC, HIPEC plays an important role in primary and recurrent ovarian cancer, and the PCI is the most important criterion in this decision.

Ovarian cancer has the highest mortality rate among gynecologic malignant tumors. Data are lacking on the survival benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) in women with ovarian cancer who underwent primary or interval cytoreductive surgery. To assess the clinical benefit of HIPEC after primary or interval maximal cytoreductive surgery in women with stage III or IV primary advanced ovarian cancer. In this single-blind randomized clinical trial performed at 2 institutions in South Korea from March 2, 2010, to January 22, 2016, a total of 184 patients with stage III or IV ovarian cancer with residual tumor size less than 1 cm were randomized (1:1) to a HIPEC (41.5 °C, 75 mg/m2 of cisplatin, 90 minutes) or control group. The primary end point was progression-free survival. Overall survival and adverse events were key secondary end points. The date of the last follow-up was January 10, 2020, and the data were locked on February 17, 2020. Hyperthermic intraperitoneal chemotherapy after cytoreductive surgery. Progression-free and overall survival. Of the 184 Korean women who underwent randomization, 92 were randomized to the HIPEC group (median age, 52.0 years; IQR, 46.0-59.5 years) and 92 to the control group (median age, 53.5 years; IQR, 47.5-61.0 years). After a median follow-up of 69.4 months (IQR, 54.4-86.3 months), median progression-free survival was 18.8 months (IQR, 13.0-43.2 months) in the control group and 19.8 months (IQR, 13.7-55.4 months) in the HIPEC group (P = .43), and median overall survival was 61.3 months (IQR, 34.3 months to not reported) in the control group and 69.5 months (IQR, 45.6 months to not reported) in the HIPEC group (P = .52). In the subgroup of interval cytoreductive surgery after neoadjuvant chemotherapy, the median progression-free survival was 15.4 months (IQR, 10.6-21.1 months) in the control group and 17.4 months (IQR, 13.8-31.5 months) in the HIPEC group (hazard ratio for disease progression or death, 0.60; 95% CI, 0.37-0.99; P = .04), and the median overall survival was 48.2 months (IQR, 33.8-61.3 months) in the control group and 61.8 months (IQR, 46.7 months to not reported) in the HIPEC group (hazard ratio, 0.53; 95% CI, 0.29-0.96; P = .04). In the subgroup of primary cytoreductive surgery, median progression-free survival was 29.7 (IQR, 17.2-90.1 months) in the control group and 23.9 months (IQR, 12.3-71.5 months) in the HIPEC group, and the median overall survival was not reached in the control group and 71.3 months (IQR, 45.6 months to not reported) in the HIPEC group. The addition of HIPEC to cytoreductive surgery did not improve progression-free and overall survival in patients with advanced epithelial ovarian cancer. Although the results are from a subgroup analysis, the addition of HIPEC to interval cytoreductive surgery provided an improvement of progression-free and overall survival. ClinicalTrials.gov Identifier: NCT01091636.

Background: Peritoneal surface malignancies (PSM) are aggressive cancers with limited treatment access in low- and middle-income countries (LMICs). While cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have improved survival outcomes globally, their feasibility in LMICs remains underexplored. This first multicenter study in North Africa evaluates the implementation and outcomes of CRS with or without HIPEC in resource-limited settings. Methods: A retrospective cohort study of 391 patients with PSM (colorectal cancer, pseudomyxoma peritonei, ovarian cancer, gastric cancer, or mesothelioma) treated with CRS ± HIPEC between 2014 and 2020 at four tertiary centers in Morocco, Tunisia, and Algeria. Primary outcomes included overall survival (OS), disease-free survival (DFS), and severe postoperative morbidity (Clavien-Dindo ≥ IIIa). Cox regression was used to identify independent prognostic factors. Results: Among 391 patients, complete cytoreduction (CC-0/1) was achieved in 88%, and HIPEC was performed in 39%. Severe morbidity occurred in 22%, with HIPEC, spleno-pancreatectomy, and incomplete cytoreduction (CC-2) identified as significant risk factors. The median OS was 68 months, with 1- and 5-year survival rates of 97% and 56%, respectively. Patients undergoing CRS + HIPEC had significantly longer OS than CRS alone (70 vs. 64 months, p = 0.016), though DFS was not significantly different between groups. Independent predictors of improved OS included HIPEC, CC score, PCI, and primary tumor type. Conclusions: This first North African multicenter study establishes the feasibility and efficacy of CRS and HIPEC in LMICs, achieving survival outcomes comparable to high-income settings. The findings support expanding advanced PSM treatment programs in resource-limited settings, emphasizing structured training and multidisciplinary collaboration to improve access and outcomes.

Response to: “Hyperthermic intraperitoneal chemotherapy in epithelial ovarian cancer should be proposed in eight time points”

Does timing of intraperitoneal chemotherapy initiation following primary cytoreductive surgery with bowel resection impact outcomes in patients with advanced ovarian cancer?

The OVHIPEC-1 trial demonstrated that adding hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery (CRS) for patients with stage III epithelial ovarian cancer results in a significant increase in recurrence-free survival and overall survival. To inform policymakers about the macroeconomic budget, we conducted a budget impact analysis. The expenditure of the Dutch health care system between 2017 and 2025 associated with the introduction of HIPEC for patients with stage III ovarian cancer eligible for interval CRS (target population) was assessed during their entire treatment course (surgical and subsequent treatment). Cost estimates are based on national registry data, national benchmark costs for hospital-related activities, list prices for drugs, therapeutic guidelines, and expert opinion. Sensitivity and scenario analyses were performed to test robustness of the analysis. The Dutch target population is expected to increase from 200 patients in 2017 to 233 patients in 2025, with 80% receiving HIPEC in 2025. Between 2017 and 2025, the impact on the annual surgical budget is €3.5 million, of which €1.8 million is directly attributable to HIPEC and its associated costs. When considering the cost of all ovarian cancer-related treatments, an additional €30,898 per HIPEC patient is spent in 2025, mainly driven by prolonged recurrence-free survival resulting in extended maintenance therapy and treatment for more platinum-sensitive recurrences. This leads to an annual total treatment budget impact of €26 million in 8 years, with €5.7 million directly associated with HIPEC use. Within the Dutch health care system, the surgical budget impact of HIPEC is acceptable and falls within the boundaries for reimbursement of the responsible decision-making bodies. The total budget impact is mostly affected by the high costs of systemic treatment after prolonged recurrence-free survival due to HIPEC.

Background: Peritoneal surface malignancies (PSMs) are a heterogenous group of primary and metastatic cancers affecting the peritoneum. They are associated with poor long-term outcomes. Many centers around the world adopt cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in routine clinical practice for these otherwise condemned patients despite a lack of high-level evidence from randomized control trials. This study aimed to investigate and present our 10-year experience with this controversial method, CRS and HIPEC, for PSM in a single tertiary center in a Baltic country. Methods: Patients who underwent CRS and HIPEC at Vilnius University Hospital Santaros Klinikos between 2011 and 2021 were included in this retrospective study. Overall survival was the primary study outcome. Secondary outcomes included postoperative morbidity and mortality, and local or systemic recurrence rates. Results: Sixty-nine patients who underwent CRS and HIPEC were included in the study. Most patients underwent treatment for peritoneal metastases from colorectal, ovarian, and appendiceal cancers. Six (8.7%) patients received CRS and HIPEC for primary peritoneal neoplasm—pseudomyxoma peritonei. The mean peritoneal carcinomatosis index score was 12 ± 7. Complete cytoreduction was achieved in 62 (89.9%) patients. The mean OS was 39 ± 29 months. The mean survival of patients with PSMs of different origin was as follows: 39 ± 25 (95% CI: 28–50) months for colorectal cancer, 44 ± 31 (95% CI: 30–58) months for ovarian cancer, 32 ± 21 (95% CI: 21–43) months for appendiceal cancer, 422 ± 1 (95% CI: 12–97) months for pseudomyxoma peritonei, and 7 months for gastric cancer. Conclusions: The current study demonstrated the results of the CRS and HIPEC program in a single Baltic country tertiary center. Patients who underwent CRS and HIPEC for PSMs achieved moderate survival rates with acceptable postoperative morbidity and mortality risk.

Splenectomy revisited in 2011: Impact on hematologic toxicities while performing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Introduction/BackgroundThe aim of the surgical treatment of advanced ovarian cancer is to completely remove all macroscopic disease.To achieve optimal cytoreduction, the use of extensive upper abdominal surgery has become widely...

Peritoneal surface malignancies have historically presented a treatment challenge for clinicians. Not infrequently, epithelial cancers can seed the peritoneal cavity. Neoplasms of the appendix can result in peritoneal dissemination of disease and pseudomyxoma peritonei; in colon cancer, up to 25% with recurrent disease will develop a peritoneal surface predominant pattern of recurrence (1), and among those resected advanced gastric cancer, the majority of patients who recur in the first five years following surgery will develop peritoneal disease (2). Among the approximately 21,290 cases of ovarian cancer cases estimated to be diagnosed in 2015 (3), most will present in an advanced disease state, many with evidence of peritoneal carcinomatosis. In addition to epithelial derived cancers, 10-15% of the approximately 2,500 cases of malignant mesothelioma diagnosed in the U.S. will develop in the peritoneal cavity (4). For all these tumor histologies, cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has been considered in the treatment algorithm for selected patients. Over time, CRS/HIPEC has seen an increased utilization in treating select patients with peritoneal disease patterns previously considered inoperable, and has been associated with favorable survival outcomes. In patients with colorectal peritoneal carcinomatosis, a recent retrospective study of 539 patients undergoing a complete cytoreduction reported a median overall survival of 32.6 months (5). No doubt these observed improved outcomes compared to historical cohorts are multifactorial, reflecting improvements in systemic therapies, refinements in surgical techniques and perioperative care, and a better understanding of tumor biology contributing to better patient selection for surgery. Nonetheless, the remarkably favorable data are compelling and speak for the importance of consideration of CRS/ HIPEC in the context of a multidisciplinary approach for patients with peritoneal surface malignancy. This issue of Journal of Gastrointestinal Oncology (JGO) focuses on CRS/HIPEC and its application for various cancers. A paper led by the editors highlight some of the important historical developments in the evolution of CRS and HIPEC. Dr. Paul Sugarbaker and colleagues share their extensive expertise discussing surgical techniques of CRS/ HIPEC and pharmacology of intraperitoneal chemotherapy, while Dr. Goodman provides an excellent review of the selection of chemotherapeutic agents used for this procedure. Dr. Low presents an interesting summary on the use of MRI in the pre-operative evaluation and surveillance of patients being considered for or treated with CRS/HIPEC. Finally, each of the five tumor histologies discussed above is considered in depth in a separate manuscript, including two original papers studying CRS/HIPEC for high grade appendiceal cancer and ovarian cancer. Also in this issue is an important section on quality issues pertaining to CRS/HIPEC, including a review paper discussing the morbidity and mortality associated with the procedure. These procedures can be extensive, and not without risk, and consideration of these factors in the clinical decision making is essential. Dr. Lambert provides a very thoughtful synopsis of the palliative role of CRS/HIPEC, and Dr. Turaga discusses the impact of surgical volume in centers of these procedures on surgical outcomes. Dr. Votanopoulos presents a review of the indications and outcomes following repeat HIPEC surgery, which can be sometimes considered in select patients. Finally, Dr. Nash discusses current