Hyperthermic Intraperitoneal Chemotherapy In Patients Research Articles

The safety and effectiveness of prophylactic hyperthermic intraperitoneal chemotherapy in patients with pathological T3-4 locally advanced colon cancer

The safety and effectiveness of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in pathological T3-4 locally advanced (pT3N+M0 and pT4NxM0) colon cancer (CC) patients with radical resection need further study. Clinical and pathological information of pT3-4 locally advanced CC patients who received radical surgery in our hospital from January 2018 to December 2020 were analyzed. The prognosis of patients was estimated using Cox proportional hazards regression analysis and Kaplan-Meier method. Among 927 patients, 10.4% (96/927) received prophylactic HIPEC based on 5-FU, 4.6% (43/927) received prophylactic HIPEC based on lobaplatin, 85.0% (788/927) received conventional therapy. The incidence of metachronous peritoneal carcinomatosis (mPC) was 9.4%. Complications occurred in 32 patients (4.1%) in the conventional therapy group, 6 patients (6.3%) in the prophylactic HIPEC group based on 5-FU and 3 patients (7.0%) in the prophylactic HIPEC group based on lobaplatin within 30 days after surgery (5-FU vs. conventional therapy group, p=0.464; Lobaplatin vs. conventional therapy group, p=0.591). Multivariate Cox regression analysis revealed that prophylactic HIPEC based on either 5-FU or lobaplatin regimen could not effectively improve mPC-free survival (5-FU: p=0.020, HR=1.927, 95% CI, 1.111-3.343; Lobaplatin: p=0.167, HR=0.247, 95% CI, 0.034-1.796), overall survival (5-FU: p=0.361, HR=1.360, 95% CI, 0.703-2.634; Lobaplatin: p=0.780, HR=0.816, 95% CI, 0.195-3.416) and disease-free survival (5-FU: p=0.525, HR=1.149, 95% CI, 0.749-1.760; Lobaplatin: p=0.117, HR=0.488, 95% CI, 0.199-1.198). Early prophylactic HIPEC based on 5-FU or lobaplatin subsequent to radical resection for patients with pT3-4 locally advanced CC is safe, but not effective in reducing the risk for mPC.

Repeat cytoreduction with Hyperthermic Intraperitoneal chemotherapy in patients with peritoneal disease: A 5-year retrospective analysis

BackgroundCytoreductive surgery with Hyperthermic Intraperitoneal Chemotherapy (CR-HIPEC) is a locorregional surgical therapy applied in patients with peritoneal-only metastatic disease of primary abdominal malignancies. Integrated in a multimodal treatment, CR-HIPEC is associated with increased overall survival. In cases of peritoneal-site only relapse, it may be carried out more than once. MethodsPatients who received a CR-HIPEC between January 2016 and December 2020 at Instituto Português de Oncologia do Porto, Portugal were included in a unicentric, retrospective, observational study. Short- and long-term outcomes after surgery were analyzed. ResultsIn this period, 259 CR-HIPEC were performed on 248 patients. Of these, 31 were CR-HIPEC repeats, with 6 being the third HIPEC in the same patient. Of the 31 cases, 15 (48.4 %) had an appendicular origin. Mean PCI in re-HIPEC group was 10.6 (SD ± 7.1). No significant differences in baseline characteristics between the first and re-HIPEC groups were found, except for mean PCI, higher in the 1st HIPEC group (p = 0.047). In re-HIPEC group, major complications rate (CT-CAE 3–4) was 12.9 % (n = 4), without postoperative mortality. The 1st and re-HIPEC group had similar morbidity rates and hospitalization time. With a median follow-up time of 44 months, relapse rate after repeat CR-HIPEC was 45.2 % (n = 14), with a mean overall survival (OS) of 68.7 months and 5-year OS of 78 %. ConclusionsRepeat CR-HIPEC is a safe approach with an acceptable complication rate for its complexity, associated with a survival benefit in selected patients. It should be presented as a valid therapeutic option in recurrent peritoneal disease.

Long‐term outcomes and survival analysis of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy in patients with pseudomyxoma peritonei at a newly established peritoneal malignancy centre in Japan

AbstractBackgroundCytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is established in the management of pseudomyxoma peritonei (PMP), selected cases of peritoneal mesothelioma, and resectable colorectal or ovarian peritoneal metastases in Western countries. However, the efficacy and feasibility of these techniques are not well established in the Asian population, and little has been reported on long‐term survival outcomes for surgically resected PMP patients.Materials and MethodsRetrospective analysis of a prospective database of short‐ and longer‐term outcomes of consecutive patients who underwent CRS and HIPEC for PMP in a newly established peritoneal malignancy unit in Japan between 2010 and 2016.ResultsA total of 105 patients underwent CRS and HIPEC and 57 maximal tumor debulking (MTD) for pseudomyxoma peritonei. In the CRS group, the primary tumor was appendiceal in 94 patients (90%) followed by ovarian and colorectal. Major postoperative complications occurred in 22/105 patients (21%) with one in‐hospital mortality (0.9%). The 5‐year overall and disease‐free survival rates for the CRS group were 74.2% and 50.1%, respectively. Multivariate analysis revealed unfavorable histology to be the significant predictor of reduced overall and disease‐free survival. Completeness of cytoreduction, CA19‐9, and CA125 were also associated with disease‐free survival.ConclusionsThis is the first report on long‐term outcomes and survival analysis of CRS and HIPEC for PMP in the Asian population. CRS and HIPEC can be conducted with reasonable safety and favorable survival in a new center. Complete tumor removal and histological type are the strongest prognostic factors for both overall and disease‐free survival.

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.

Prophylactic Hyperthermic Intraperitoneal Chemotherapy for Patients at High Risk of Developing Gallbladder Cancer Peritoneal Metastases: Case Report and Rationale for a Prospective Clinical Trial

Gallbladder cancer is a devastating disease with a 5-year survival of only 18%. The majority of gallbladder cancers are discovered incidentally in patients undergoing cholecystectomy. During non-oncologic laparoscopic cholecystectomy for gallbladder disease, gallbladder perforation occurs in 29% of cases and spillage of gallstones occurs in 9% of cases. Patients with gallbladder cancer frequently develop peritoneal recurrence, particularly after intra-operative bile spillage during cholecystectomy for incidental gallbladder cancer. The high likelihood of spillage and peritoneal seeding during cholecystectomy for incidental gallbladder cancer suggests the need for prophylactic strategies to prevent peritoneal carcinomatosis. Hyperthermic intraperitoneal chemotherapy (HIPEC) has efficacy in gallbladder cancer patients with macroscopic peritoneal disease undergoing cytoreductive surgery and has been associated with a survival advantage in a multi-institutional retrospective case series. However, the utilization of HIPEC with a prophylactic intent against the development of peritoneal disease following resection of gallbladder cancer has not yet been prospectively studied. Here, we review the literature surrounding gallbladder cancer and HIPEC, report an institutional experience utilizing prophylactic HIPEC, and discuss a recently proposed prospective clinical trial evaluating the efficacy of prophylactic HIPEC in the prevention of gallbladder peritoneal metastasis.

Hyperthermic intraperitoneal chemotherapy in patients with incomplete cytoreduction for appendiceal pseudomyxoma peritonei: a 10-year treatment experience in China

BackgroundTo explore the application value of hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with incomplete cytoreduction for appendiceal pseudomyxoma peritonei (PMP).MethodsWe retrospectively analyzed the clinical data of 526 patients with incomplete cytoreduction for appendiceal PMP to discover its prognostic factors, and the therapeutic value of HIPEC.ResultsThe 5-year and 10-year overall survival rates of patients after cytoreductive surgery (CRS) treated with HIPEC were significantly higher than those without HIPEC (5y-OS: 58% vs. 48%, 10y-OS: 37% vs. 16%, P = 0.032). The median progression-free survival (PFS) following CRS was 20 months, with a 20% 3-year PFS. The median PFS following CRS + HIPEC was 33 months, with a 60% 3-year PFS (P = 0.000). Univariate analysis indicated that HIPEC, gender, completeness of cytoreduction (CCR) and pathological grade had statistical difference. Multivariate analysis showed that CRS without HIPEC and high pathological grade were independent risk factors for poor prognosis and rapid tumor progression.ConclusionsHIPEC may prolong the survival in patients with incomplete cytoreduction for low-grade appendiceal PMP. High pathological grade indicates poor survival and rapid tumor progression.

Secondary cytoreductive surgery with and without hyperthermic intraperitoneal chemotherapy for recurrent ovarian cancer.

Secondary cytoreductive surgery (CRS) can afford promising results in patients with recurrent ovarian cancer; however, the impact of hyperthermic intraperitoneal chemotherapy (HIPEC) remains unclear. We compared the outcomes of secondary CRS combined with and without HIPEC in patients with recurrent ovarian cancer. We retrospectively evaluated patients with recurrent ovarian cancer who underwent secondary CRS, with or without HIPEC (n=46), at the Yonsei Cancer Center between January 2006 and February 2021. Of the 46 included patients, 20 underwent secondary CRS-plus-HIPEC, while 26 underwent secondary CRS without HIPEC (henceforth referred to as secondary CRS-only). Of the 46 patients, 84.8% and 89.1% had undergone optimal surgery and platinum-based chemotherapy, respectively, as the initial treatment before the first relapse. Overall, 32.6% of patients received maintenance therapy, such as bevacizumab or polyadenosine diphosphate ribose polymerase inhibitors. The median follow-up period was 15.9 months. The median progression-free survival (PFS) was 32.7 and 25.1 months in the secondary CRS-plus-HIPEC and secondary CRS-only groups, respectively; however, both groups failed to reach the median overall survival (OS). Based on the Kaplan-Meier analysis, there was no difference in PFS (P=0.587) or OS (P=0.239) between the two groups. We identified patients with epithelial ovarian cancer and found that the median PFS was 25.1 months in the secondary CRS-only group; this was not achieved in the secondary CRS-plus-HIPEC group (P=0.244). In patients with recurrent ovarian cancer, secondary CRS with HIPEC did not improve survival when compared with CRS without HIPEC. However, on subgrouping patients with epithelial ovarian cancer, the addition of HIPEC to secondary CRS tended to improve PFS.

Actual 5-Year Survival After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Patients with Peritoneal Carcinomatosis of Colorectal Origin.

Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) improves survival compared with chemotherapy alone in patients with peritoneal carcinomatosis (PC) of colorectal (CRC) origin, however, long-term survival data are lacking. We report the actual survival of patients who underwent CRS/HIPEC for PC of CRC origin with a minimum potential 5-year follow-up period to identify factors that preclude long-term survival. We performed a retrospective analysis of a prospective database, analyzing patients undergoing CRS/HIPEC for PC of CRC origin from 2007 to 2017. Patients with aborted CRS/HIPEC, postoperative follow-up <90 days, or non-CRC histology were excluded. Overall survival (OS) and disease-free survival (DFS) were measured from date of surgery. Surviving patients with <60 months of follow-up were censored at date of last follow-up. A total of 103 patients met inclusion criteria and were analyzed. CC score 0-1 was achieved in 89.3% of patients, and median peritoneal cancer index (PCI) was 9 (interquartile range [IQR] 5-17). Ninety-day mortality was 2.9%. The median follow-up of survivors was 88 months. Five-year OS was 36%, and median OS was 42.5 months. Factors independently associated with poor survival included high PCI (PCI = 14-20, hazard ratio [HR] 3.1, p = 0.007, and PCI > 20, HR 5.3, p ≤ 0.001) and incomplete CRS (CC score-2, HR 2.96, p = 0.02). Patients with low PCI (0-6) had 5-year OS 60.7%. Actual 5-year OS was 36% and median OS was 42.5 months. Our study demonstrates that patients with PC from CRC origin with low PCI who undergo complete surgical resection can achieve favorable long-term survival.

Outcomes Following Cytoreductive Surgery and Hyperthermic Intraoperative Thoraco-Abdominal Chemotherapy with Diaphragm Resection for Peritoneal Carcinomatosis: A Retrospective Cohort Study.

We aimed to evaluate the safety and efficacy of hyperthermic intraoperative thoraco-abdominal chemotherapy (HITAC) and cytoreductive surgery (CRS) for peritoneal carcinomatosis (PC) patients who underwent diaphragm resection. PC patients who underwent CRS with diaphragm resection were selected from a prospectively established database and were divided into hyperthermic intraperitoneal chemotherapy (HIPEC) and HITAC groups. The clinicopathological characteristics, treatment-related variables, perioperative adverse events (AEs), and survival outcomes were compared between the two groups. Of 1168 CRS + HIPEC/HITACs, 102 patients were enrolled-61 HITAC patients and 41 HIPEC patients. In the HITAC and HIPEC groups, the incidence of grade III-V AEs was 29.5% versus 34.1% (p = 0.621). The pleural progression rates were 13.2 versus 18.9% (p = 0.462) and the median overall survival (OS) was 50.5 versus 52.7 months (p = 0.958). Median time to progression (TTP) in thoracic disease was not reached. There was no significant difference in perioperative AEs, TTP, and OS for total patients and the completeness of cytoreduction (CC) score subgroups (p > 0.05). Age ≥ 60years (hazard ratio [HR] 4.162, p = 0.026) was an independent risk factor influencing pleural progression, and primary malignant peritoneal mesothelioma (MPM; HR 2.749, p = 0.016) and the presence of two or more serious AEs (SAEs; HR 7.294, p = 0.001) were independent risk factors influencing OS. HITAC can be performed in carefully selected PC patients who underwent diaphragm resection, with no worsening of the safety profile and a possible benefit for pleural progression. In those patients, age ≥ 60 years is associated with a shorter TTP of thoracic disease, while primary MPM and two or more perioperative SAEs are associated with worse OS.

Current Evidence for the Use of HIPEC and Cytoreductive Surgery in Gastric Cancer Metastatic to the Peritoneum.

Gastric cancer (GCa) is an aggressive malignancy, representing the third leading cause of cancer mortality worldwide. The poor prognosis of GCa can be associated with the prevalence of peritoneal metastasis (PM). Current international and national GCa treatment guidelines only recommend palliative treatment options for patients with PM. Since the 1980s there have been multiple single arm trials, randomized controlled trials, and metanalysis investigating the use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with advanced GCa, with or without PM. Results from these studies have been encouraging, with some large-volume centers even incorporating HIPEC into their treatment algorithms for patients with advanced GCa. Additionally, there are several ongoing trials that, when completed, will increase our understanding of the efficacy of CRS & HIPEC in patients with GCa metastatic to the peritoneum. Herein we review the current evidence, ongoing trials, consensus guidelines, and future considerations regarding the use of CRS & HIPEC in patients suffering from GCa with PM.

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.

Etiological analysis of infection after CRS + HIPEC in patients with PMP

BackgroundCytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is the standard treatment for pseudomyxoma peritonei (PMP). It can significantly prolong the survival of patients, but at the same time may increase the risk of postoperative infection.MethodPatients with PMP who underwent CRS + HIPEC at our center were retrospectively analyzed. According to PMP patients, basic clinical data and relevant information of postoperative infection, we analyzed the common sites of postoperative infection, results of microbial culture and the antibiotics sensitivity. Univariate and multivariate analysis were performed to explore infection-related risk factors.ResultAmong the 482 patients with PMP, 82 (17.0%) patients were infected after CRS + HIPEC. The most common postoperative infection was central venous catheter (CVC) infection (8.1%), followed by abdominal-pelvic infection (5.2%). There were 29 kinds of microbes isolated from the culture (the most common was Staphylococcus epidermidis), including 13 kinds of Gram-positive bacteria, 12 kinds of Gram-negative bacteria, and 4 kinds of funguses. All the antibiotics sensitivity results showed that the most sensitive antibiotics were vancomycin to Gram-positive bacteria (98.4%), levofloxacin to Gram-negative bacteria (68.5%), and fluconazole to fungus (83.3%). Univariate and multivariate analysis revealed the infection independent risk factors as follow: intraoperative blood loss ≥ 350 mL (P = 0.019), ascites volume ≥ 300 mL (P = 0.008).ConclusionPMP patients may have increased infection risk after CRS + HIPEC, especially CVC, abdominal-pelvic and pulmonary infections. The microbial spectrum and antibiotics sensitivity results could help clinicians to take prompt prophylactic and therapeutic approaches against postoperative infection for PMP patients.

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).

Hyperthermic Intraperitoneal Chemotherapy After Interval Cytoreductive Surgery for Patients With Advanced-Stage Ovarian Cancer Who Had Received Neoadjuvant Chemotherapy

Hyperthermic intraperitoneal chemotherapy (HIPEC) followed by interval cytoreductive surgery (ICS) has shown survival benefits for patients with advanced-stage ovarian cancer. However, there is still a lack of consensus regarding the integration of HIPEC into clinical practice. To evaluate the safety and effectiveness of ICS with HIPEC compared with ICS alone in clinical practice for patients with advanced-stage ovarian cancer. This prospective, multicenter, comparative effectiveness cohort study enrolled 205 patients with stage III or IV ovarian cancer who had received at least 3 cycles of neoadjuvant chemotherapy followed by ICS with HIPEC or ICS without HIPEC at 7 Korean Gynecologic Oncology Group institutions between September 1, 2017, and April 22, 2022. Nine patients were excluded because they did not meet the inclusion criteria. Neoadjuvant chemotherapy followed by ICS with HIPEC or ICS without HIPEC. The primary end point was progression-free survival (PFS). Overall survival (OS) and the safety profile were the key secondary end points. This study included 196 patients (median age, 58.0 years [range, 38-82 years]), of whom 109 underwent ICS with HIPEC and 87 underwent ICS without HIPEC. The median duration of follow-up was 28.2 months (range, 3.5-58.6 months). Disease recurrence occurred in 128 patients (65.3%), and 30 patients (15.3%) died. Interval cytoreductive surgery with HIPEC was associated with a significant improvement in median PFS compared with ICS without HIPEC (22.9 months [95% CI, 3.5-58.6 months] vs 14.2 months [95% CI, 4.0-56.2 months]; P = .005) and median OS (not reached [95% CI, 3.5 months to not reached] vs 53.0 [95% CI, 4.6-56.2 months]; P = .002). The frequency of grade 3 or 4 postoperative complications was similar in both groups (ICS with HIPEC, 3 of 109 [2.8%] vs ICS without HIPEC, 3 of 87 [3.4%]; P > .99). Among patients with recurrence, the frequency of peritoneal recurrence was lower in the ICS with HIPEC group than in the ICS without HIPEC group (21 of 64 [32.8%] vs 41 of 64 [64.1%]; P = .001). This study suggests that ICS in conjunction with HIPEC was associated with longer PFS and OS than ICS without HIPEC for patients with advanced-stage ovarian cancer and was not associated with higher rates of postoperative complications. The lower rate of peritoneal recurrence after HIPEC may be associated with improved OS.

Adjuvant dendritic cell-based immunotherapy after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with malignant peritoneal mesothelioma: a phase II clinical trial

BackgroundMalignant peritoneal mesothelioma (MPM) is an aggressive malignancy with a poor prognosis. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival outcomes, but recurrence rates remain high. Dendritic cell-based...

A global analysis of nutrition support practices in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignancy

Perioperative nutritional care has been identified as an important factor in the management of patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Nevertheless, there is no published consensus on best practice for nutritional management specific to this patient group. The purpose of this study was to identify the current nutrition care practices among international centres performing CRS and HIPEC for patients with peritoneal malignancy. An online survey was developed and sent to experienced CRS and HIPEC centres. The survey questions covered clinician and institution demographics, formal nutrition care pathways, pre-operative nutrition care, post-operative nutrition support and post-discharge nutritional follow-up. Eighty-two centres were contacted, and 42 responses were received. Respondents were from 20 different countries and were mostly dietitians (71%). Nutrition assessments were frequently completed (52% pre-operatively and 86% post-operatively) and most centres used a validated nutrition screening or assessment tool (79%). Perioperative nutrition support with respect to the use of enteral nutrition, parenteral nutrition and enhanced recovery after surgery varied widely between centres. The use of routine parenteral and enteral nutrition was significantly higher in Europe compared with other locations (p=0.028). Nutrition care is pivotal and has been positively integrated into the complex management of patients undergoing CRS and HIPEC globally, however variation in practice is evident. The findings highlight a unique opportunity to collaboratively investigate the role nutrition plays in determining outcomes and to identify the most appropriate nutrition support methods to achieve improved clinical outcomes for these high-risk patients.

HIPEC in Ovarian Cancer Is the Future… and Always Will Be? Results from a Spanish Multicentric Survey.

Ovarian cancer is the leading cause of death due to gynecological tumors in the female population. Despite optimal first-line treatment, including cytoreduction and platinum-based systemic chemotherapy, recurrences are frequent. The use of hyperthermic intraperitoneal chemotherapy (HIPEC) has been criticized, especially because of the lack of randomized controlled trials (RCTs) with convincing results to support the use of HIPEC in patients with ovarian cancer with peritoneal dissemination. In 2018, the clinical trial published by Van Driel et al. reported improved outcomes in favor of HIPEC treatment with cisplatin. In this study, we conducted a national survey within the Spanish group of peritoneal surgical oncology (Grupo Español de Cirugía Oncológica Peritoneal, GECOP) to explore the impact of the results of this RCT on clinical practice. A total of 33 groups completed the survey. Routine clinical practice was not changed in 28 of the 33 groups (85%) based on the results of the Van Driel trial. Despite the results of this RCT, most groups considered that more RCTs are needed and that, in the future, HIPEC may become the standard of care. In conclusion, the results from RCTs evaluating HIPEC treatment in patients with ovarian cancer has not been transferred to clinical practice.

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 .

A retrospective analysis of secondary cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy in patients with recurrent ovarian cancer.

To evaluate the effect of secondary cytoreductive surgery (SeCRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent epithelial ovarian cancer patients. This retrospective study analyzed a prospective database. We collected information of 389 patients who were diagnosed with recurrent epithelial ovarian cancer. All patients underwent SeCRS with or without HIPEC. Overall survival and progression-free survival (PFS) were used to evaluate the treatment effectiveness. Of the 389 patients collected, 123 underwent primary or interval cytoreductive surgery at initial treatment and SeCRS at recurrence (Group A), 130 underwent primary or interval cytoreductive surgery at initial and SeCRS plus HIPEC at recurrence (Group B), and 136 underwent primary or interval cytoreductive surgery plus HIPEC at initial and SeCRS plus HIPEC at recurrence (Group C). The median overall survival for Groups A, B, and C were 49.1 months (95% confidence interval [CI]: 47.6-50.5), 56.0 months (95% CI: 54.2-57.7), and 64.4 months (95% CI: 63.1-65.6), respectively. The median PFS for Groups A, B, and C were 13.1 months (95% CI: 12.6-13.5), 15.0 months (95% CI: 14.2-15.7), and 16.8 months (95% CI: 16.1-17.4), respectively. There were no significant difference in incidence and grade of adverse events among groups. This study suggested that SeCRS plus HIPEC followed by chemotherapy resulted in longer overall survival and PFS than only SeCRS followed by chemotherapy in patients with recurrent ovarian cancer, especially in patients who were treated with repeat HIPEC.

Efficacy and Safety of Intraoperative Hyperthermic Intraperitoneal Chemotherapy for Locally Advanced Colon Cancer

Peritoneal metastasis in patients with locally advanced colon cancer (T4 stage) is estimated to recur at a rate of approximately 25% at 3 years from surgical resection and is associated with poor prognosis. There is controversy regarding the clinical benefit of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in these patients. To assess the efficacy and safety of intraoperative HIPEC in patients with locally advanced colon cancer. This open-label, phase 3 randomized clinical trial was conducted in 17 Spanish centers from November 15, 2015, to March 9, 2021. Enrolled patients were aged 18 to 75 years with locally advanced primary colon cancer diagnosed preoperatively (cT4N02M0). Patients were randomly assigned 1:1 to receive cytoreduction plus HIPEC with mitomycin C (30 mg/m2 over 60 minutes; investigational group) or cytoreduction alone (comparator group), both followed by systemic adjuvant chemotherapy. Randomization of the intention-to-treat population was done via a web-based system, with stratification by treatment center and sex. The primary outcome was 3-year locoregional control (LC) rate, defined as the proportion of patients without peritoneal disease recurrence analyzed by intention to treat. Secondary end points were disease-free survival, overall survival, morbidity, and rate of toxic effects. A total of 184 patients were recruited and randomized (investigational group, n = 89; comparator group, n = 95). The mean (SD) age was 61.5 (9.2) years, and 111 (60.3%) were male. Median duration of follow-up was 36 months (IQR, 27-36 months). Demographic and clinical characteristics were similar between groups. The 3-year LC rate was higher in the investigational group (97.6%) than in the comparator group (87.6%) (log-rank P = .03; hazard ratio [HR], 0.21; 95% CI, 0.05-0.95). No differences were observed in disease-free survival (investigational, 81.2%; comparator, 78.0%; log-rank P = .22; HR, 0.71; 95% CI, 0.41-1.22) or overall survival (investigational, 91.7%; comparator, 92.9%; log-rank P = .68; HR, 0.79; 95% CI, 0.26-2.37). The definitive subgroup with pT4 disease showed a pronounced benefit in 3-year LC rate after investigational treatment (investigational: 98.3%; comparator: 82.1%; log-rank P = .003; HR, 0.09; 95% CI, 0.01-0.70). No differences in morbidity or toxic effects between groups were observed. In this randomized clinical trial, the addition of HIPEC to complete surgical resection for locally advanced colon cancer improved the 3-year LC rate compared with surgery alone. This approach should be considered for patients with locally advanced colorectal cancer. ClinicalTrials.gov Identifier: NCT02614534.