In patients with resectable colorectal peritoneal metastases, it is unclear whether systemic chemotherapy, in addition to cytoreductive surgery-hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), improves overall survival (OS). This systematic review of 12 retrospective studies involving 3721 patients aimed to summarize the available evidence. Contradictory results were found regarding the effectiveness of neoadjuvant, adjuvant, and perioperative systemic therapies on OS, with a high risk of bias. Available evidence remains inconclusive, stressing the need for prospective, randomized trials, like the ongoing Dutch CAIRO6-trial.

UNASSIGNED: We compared the relative benefits, harms and cost-effectiveness of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery ± systemic chemotherapy versus cytoreductive surgery ± systemic chemotherapy or systemic chemotherapy alone in people with peritoneal metastases from colorectal, gastric or ovarian cancers by a systematic review, meta-analysis and model-based cost-utility analysis.
UNASSIGNED: We searched MEDLINE, EMBASE, Cochrane Library and the Science Citation Index, ClinicalTrials.gov and WHO ICTRP trial registers until 14 April 2022. We included only randomised controlled trials addressing the research objectives. We used the Cochrane risk of bias tool version 2 to assess the risk of bias in randomised controlled trials. We used the random-effects model for data synthesis when applicable. For the cost-effectiveness analysis, we performed a model-based cost-utility analysis using methods recommended by The National Institute for Health and Care Excellence.
UNASSIGNED: The systematic review included a total of eight randomised controlled trials (seven randomised controlled trials, 955 participants included in the quantitative analysis). All comparisons other than those for stage III or greater epithelial ovarian cancer contained only one trial, indicating the paucity of randomised controlled trials that provided data. For colorectal cancer, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably results in little to no difference in all-cause mortality (60.6% vs. 60.6%; hazard ratio 1.00, 95% confidence interval 0.63 to 1.58) and may increase the serious adverse event proportions compared to cytoreductive surgery ± systemic chemotherapy (25.6% vs. 15.2%; risk ratio 1.69, 95% confidence interval 1.03 to 2.77). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to fluorouracil-based systemic chemotherapy alone (40.8% vs. 60.8%; hazard ratio 0.55, 95% confidence interval 0.32 to 0.95). For gastric cancer, there is high uncertainty about the effects of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy versus cytoreductive surgery + systemic chemotherapy or systemic chemotherapy alone on all-cause mortality. For stage III or greater epithelial ovarian cancer undergoing interval cytoreductive surgery, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to cytoreductive surgery + systemic chemotherapy (46.3% vs. 57.4%; hazard ratio 0.73, 95% confidence interval 0.57 to 0.93). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy may not be cost-effective versus cytoreductive surgery + systemic chemotherapy for colorectal cancer but may be cost-effective for the remaining comparisons.
UNASSIGNED: We were unable to obtain individual participant data as planned. The limited number of randomised controlled trials for each comparison and the paucity of data on health-related quality of life mean that the recommendations may change as new evidence (from trials with a low risk of bias) emerges.
UNASSIGNED: In people with peritoneal metastases from colorectal cancer with limited peritoneal metastases and who are likely to withstand major surgery, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should not be used in routine clinical practice (strong recommendation). There is considerable uncertainty as to whether hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy or cytoreductive surgery + systemic chemotherapy should be offered to patients with gastric cancer and peritoneal metastases (no recommendation). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should be offered routinely to women with stage III or greater epithelial ovarian cancer and metastases confined to the abdomen requiring and likely to withstand interval cytoreductive surgery after chemotherapy (strong recommendation).
UNASSIGNED: More randomised controlled trials are necessary.
UNASSIGNED: This study is registered as PROSPERO CRD42019130504.
UNASSIGNED: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/135/02) and is published in full in Health Technology Assessment; Vol. 28, No. 51. See the NIHR Funding and Awards website for further award information.
Cancers of the bowel, ovary or stomach can spread to the lining of the abdomen (‘peritoneal metastases’). Chemotherapy (the use of drugs that aim to kill cancer cells) given by injection or tablets (‘systemic chemotherapy’) is one of the main treatment options. There is uncertainty about whether adding cytoreductive surgery (cytoreductive surgery; an operation to remove the cancer) and ‘hyperthermic intraoperative peritoneal chemotherapy’ (warm chemotherapy delivered into the lining of the abdomen during cytoreductive surgery) are beneficial. We reviewed all the information from medical literature published until 14 April 2022, to answer the above uncertainty. We found the following from eight trials, including about 1000 participants. In people with peritoneal metastases from bowel cancer, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably does not provide any benefits and increases harm compared to cytoreductive surgery + systemic chemotherapy, while cytoreductive surgery + systemic chemotherapy appears to increase survival compared to systemic chemotherapy alone. There is uncertainty about the best treatment for people with peritoneal metastases from stomach cancer. In women with peritoneal metastases from ovarian cancer who require systemic chemotherapy before cytoreductive surgery to shrink the cancer to allow surgery (‘advanced ovarian cancer’), hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably increases survival compared to cytoreductive surgery + systemic chemotherapy. In people who can withstand a major operation and in whom cancer can be removed, cytoreductive surgery + systemic chemotherapy should be offered to people with peritoneal metastases from bowel cancer, while hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should be offered to women with peritoneal metastases from ‘advanced ovarian cancer’. Uncertainty in treatment continues for gastric cancer. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/135/02) and is published in full in Health Technology Assessment; Vol. 28, No. 51. See the NIHR Funding and Awards website for further award information.

BACKGROUND: To improve care for patients with colorectal peritoneal metastases (CRC-PM) or pseudomyxoma peritonei (PMP), the Dutch CRS-HIPEC quality registry was initiated in 2019. The aims are to describe the development and content of this registry and to give insight into the data collected during the first years.
METHODS: The registry is an observational cohort in the Netherlands. All patients with CRC-PM or PMP who intend to undergo cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) from 6 hospitals are included. Clinical data and outcomes (including hospital variation) were analyzed.
RESULTS: In 2019-2022, 889 patients were included in the CRS-HIPEC quality registry: 749 (84 %) with CRC-PM and 140 (16 %) with PMP. Peritoneal metastases were diagnosed synchronously in 51 % of CRC-PM patients and in 94 % of PMP patients. In patients undergoing complete CRS, the median peritoneal cancer index was 8 (IQR 4-13) for CRC-PM and 15 (IQR 6-26) for PMP. Complete cytoreduction was achieved in 639 CRC-PM patients (97 %) and 108 PMP patients (82 %). HIPEC was mainly performed with mitomycin C (CRC-PM: 94 %, PMP: 92 %). Major postoperative complications (Clavien-Dindo grade ≥3) occurred in 148 CRC-PM patients (22 %) and 30 PMP patients (23 %) with 90-day mortality rates of 2 %. In CRC-PM, differences between hospitals were observed regarding proportions of diagnostic laparoscopies/laparotomies, (neo)adjuvant treatment, ostomy formations and re-admissions.
CONCLUSIONS: The CRS-HIPEC quality registry provides insight into the outcomes of CRS-HIPEC and enables clinical auditing and observational cohort studies aiming to improve treatment outcomes for patients with CRC-PM and PMP.

Despite advances in systemic chemotherapy, patients with gastric cancer (GC) and peritoneal metastases (PMs) continue to have poor prognoses. Intraperitoneal (IP) administration of Paclitaxel (PTX) combined with systemic chemotherapy shows promise in treating PMs from GC. However, methods of drug administration need to be optimized to maximize efficacy. In this study, we utilized a mouse model with PMs derived from a human GC cell line, administering PTX either IP or intravenously (IV), and Carboplatin (CBDCA) IV 0, 1, and 4 days after PTX administration. The PMs were resected 30 min later, and concentrations of PTX and CBDCA in resected tumors were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results indicated that PTX concentrations were higher with IP administration than with IV administration, with significant differences observed on days 0 and 1. CBDCA concentrations 4 days post-IP PTX administration were higher than with simultaneous IV PTX administration. These findings suggest that IP PTX administration enhances CBDCA concentration in peritoneal tumors. Therefore, sequential IV administration of anti-cancer drugs appears more effective than simultaneous administration with IP PTX, a strategy that may improve prognoses for patients with PMs.

BACKGROUND: The PRECINCT (Pattern of peritoneal dissemination and REsponse to systemic Chemotherapy IN Common and uncommon peritoneal Tumors) is a prospective, multicenter, observational study. This report from phase I of PRECINCT outlines variations in recording the surgical peritoneal cancer index (sPCI) at experienced peritoneal malignancy centers and the incidence of pathologically confirmed disease in morphologically different peritoneal lesions (PL).
METHODS: The sPCI was recorded in a prespecified format that included the morphological appearance of PL. Six prespecified morphological terms were provided. The surgical and pathological findings were compared.
RESULTS: From September 2020 to December 2021, 707 patients were enrolled at 10 centers. The morphological details are routinely recorded at two centers, structure bearing the largest nodule, and exact size of the largest tumor deposit in each region at four centers each. The most common morphological terms used were normal peritoneum in 3091 (45.3%), tumor nodules in 2607 (38.2%) and confluent disease in 786 (11.5%) regions. The incidence of pathologically confirmed disease was significantly higher in \'tumor nodules\' with a lesion score of 2/3 compared with a lesion score of 1 (63.1% vs. 31.5%; p < 0.001). In patients receiving neoadjuvant chemotherapy, the incidence of pathologically confirmed disease did not differ significantly from those undergoing upfront surgery [751 (47.7%) and 532 (51.4%) respectively; p = 0.069].
CONCLUSIONS: The sPCI was recorded with heterogeneity at different centers. The incidence of pathologically confirmed disease was 49.2% in \'tumor nodules\'. Frozen section could be used more liberally for these lesions to aid clinical decisions. A large-scale study involving pictorial depiction of different morphological appearances and correlation with pathological findings is indicated.

OBJECTIVE: Intraperitoneal chemotherapy can be administered as a single dose associated with hyperthermia (HIPEC) or in successive doses under normothermic conditions, such as early postoperative intraperitoneal chemotherapy (EPIC) or normothermic intraperitoneal chemotherapy (NIPEC or NIPEC-LT). Repetitive administration of intraperitoneal chemotherapy over a prolonged period may be associated with catheter-related complications, which are the primary cause of treatment interruption. This study aims to introduce and evaluate an innovative catheter system designed to mitigate these issues.
METHODS: Using a porcine experimental model, we tested a new catheter for long-term intraperitoneal access. Sixteen animals underwent catheter implantation followed by normothermic recirculation of peritoneal dialysis solution. Catheter functionality and any complications were monitored throughout successive treatment cycles.
RESULTS: The new catheter system demonstrated optimal recirculation and maintained its functionality throughout successive treatments, without complications. Catheter replacement with a guidewire was successful, ensuring continued efficacy.
CONCLUSIONS: The innovative catheter system shows promise in reducing complications and improving compliance in successive intraperitoneal chemotherapy doses, justifying further clinical trials to confirm its efficacy in patients.

BACKGROUND: Since 2016, staging laparoscopy has been implemented in the diagnostic workup of patients with gastric cancer. Staging laparoscopy aims to detect incurable disease (peritoneal metastases and irresectable tumors) and to prevent futile laparotomies.
METHODS: In this population-based nationwide study, we sought patient- and tumor characteristics associated with undergoing a staging laparoscopy. Additionally, we analyzed the prevalence of synchronous peritoneal metastases, the outcome of the staging laparoscopy and its clinical impact on treatment decisions. All patients diagnosed with non-cardia gastric cancer from the Netherlands Cancer Registry between 2016 and 2021 were included.
RESULTS: Alongside tumor characteristics, patient characteristics such as younger age, absence of comorbidities and lower WHO performance status were associated with performing a staging laparoscopy. In the study period, an increase in the proportion of patients who underwent a staging laparoscopy was observed, from 19.6% in 2016 to 32.3% in 2021 (p-value<0.001). In the same period, the prevalence of synchronous peritoneal metastases increased from 25% to 31%. In 37.6% of the patients who had the outcome of their staging laparoscopy reported, had incurable disease diagnosed during staging laparoscopy. Significantly less of these patients were treated with triplet regimens as compared to patients with a negative staging laparoscopy (18.5 vs. 76.3%; p-value<0.001).
CONCLUSIONS: The implementation of staging laparoscopy in gastric cancer patients paralleled the increase in diagnosis of incurable disease and a decrease in the application of triplet systemic therapies in these patients.

Palliative systemic treatment is currently standard of care for metastatic gastric cancer. However, patients with peritoneal metastases of gastric origin are often underrepresented in clinical studies due to unmeasurable radiologic disease. This study describes the systemic treatment strategies and outcomes in patients with peritoneal metastases in a nationwide real-world setting.
Patients with gastric adenocarcinoma and synchronous peritoneal metastases (with or without other metastases) diagnosed in the Netherlands between 2015 and 2020 were identified from the nationwide Netherlands Cancer Registry. Median overall survival (OS) and time-to-treatment failure were determined and multivariable Cox regression analyses were used to compare treatment groups, corrected for relevant tumor and patient characteristics.
In total, 1,972 patients were included, of whom 842 (43%) were treated with palliative systemic therapy. The majority received capecitabine + oxaliplatin (CAPOX; 44%), followed by fluorouracil/leucovorin/oxaliplatin (FOLFOX; 19%), and epirubicin + capecitabine + oxaliplatin (EOX; 8%). Of the 99 (45%) patients who received second-line systemic treatment, ramucirumab + paclitaxel were administered most frequently (63%). After adjustment for sex, age, comorbidities, performance status, tumor location, Lauren classification, and the presence of metastases outside of the peritoneum, patients treated with a triplet containing docetaxel and those treated with a regimen containing trastuzumab had a significantly longer OS compared with patients treated with a doublet containing a fluoropyrimidine derivate + oxaliplatin (hazard ratio [HR], 0.69; 95% CI, 0.52-0.91, and HR, 0.68; 95% CI, 0.51-0.91, respectively). Monotherapy was associated with a shorter OS (HR, 2.08, 95% CI, 1.53-2.83).
There is substantial heterogeneity in systemic treatment choices in patients with gastric cancer and peritoneal metastases in the Netherlands. In this study, patients treated with triplets containing docetaxel and with trastuzumab-containing regimens survived longer than patients who received doublet therapy. Despite this, median OS for all treatment groups remained below one year.

Multimodal treatment in peritoneal metastases (PM) from colorectal neoplasms may improve overall survival (OS). In this study, we reported our experience in using cytoreductive surgery (CRS) combined with intraperitoneal chemohyperthermia (HIPEC) for the treatment of peritoneal metastases (PM) from colorectal neoplasms. The first aim was to evaluate the overall survival of these patients. Furthermore, using the results of the Prodige 7 Trial and incorporating them with the entropy balance statistical tool, we generated a pseudopopulation on which to test the use of CRS alone. We performed a retrospective analysis based on a prospective database of all 55 patients treated with CRS + HIPEC between March 2004 and January 2023. The median OS was 47 months, with 1-, 3- and 5-year survival rates of 90.8%, 58.7% and 42.7%, respectively. There was no significant difference in the data in the pseudogroup generated with entropy balance. This finding confirms the critical role of complete cytoreduction in achieving the best OS for patients with PM. PCI > 6 seems to be the most important prognostic factor influencing OS. At present, CRS + HIPEC seems to be the therapeutic strategy that guarantees the best results in terms of OS for patients with relatively low PCI and in whom a CCS ≤ 1 can be achieved.

This manuscript reports the results of an international consensus on technologies of hyperthermic intraperitoneal perioperative chemotherapy (HIPEC) performed with the following goals: To provide recommendations for the technological parameters to perform HIPEC. To identify the role of heat and its application forms in treating peritoneal metastases. To provide recommendations regarding the correct dosimetry of intraperitoneal chemotherapy drugs and their carrier solutions. To identify for each intraperitoneal chemotherapy regimen the best dosimetry and fractionation. To identify areas of future research pertaining to HIPEC technology and regimens. This consensus was performed by the Delphi technique and comprised two rounds of voting. In total, 96 of 102 eligible panelists replied to both Delphi rounds (94.1%) with a consensus of 39/51 questions on HIPEC technical aspects. Among the recommendations that met with the strongest consensus were those concerning the dose of HIPEC drug established in mg/m2, a target temperature of at least 42°C, and the use of at least three temperature probes to pursue hyperthermia. Ninety minutes as the ideal HIPEC duration seemed to make consensus. These results should be considered when designing new clinical trials in patients with peritoneal surface malignancies.