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

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Preoperative CA 19-9 Predicts Disease Progression in Colorectal Peritoneal Metastases Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: An Analysis from the US HIPEC Collaborative.

INTRODUCTION: Patients with colorectal peritoneal metastases (CRPM) are increasingly treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Unfortunately, data identifying preoperative risk factors for poor oncologic outcomes after this procedure are limited. We aimed to determine the prognostic value of preoperative CEA, CA 125, and CA 19-9 on disease progression after CRS/HIPEC. METHODS: Patients with CRPM treated with curative intent CRS/HIPEC from 12 participating sites in the United States from 2000 to 2017 were identified. Progression-free survival (PFS), defined as disease progression or recurrence, was the primary outcome. RESULTS: In 279 patients who met inclusion criteria, the rate of disease progression was 63.8%, with a median PFS of 11 months (interquartile range [IQR] 5-20). Elevated CA 19-9 was associated with dismal PFS at 2 years (8.9% elevated vs. 30% not elevated, p < 0.01). In 113 patients who underwent upfront CRS/HIPEC, CA 19-9 emerged as the sole tumor marker independently predictive of worse PFS (hazard ratio [HR] 2.88, p = 0.048). In the subgroup of patients who had received neoadjuvant therapy (NAT), no variable was independently predictive of PFS. CA 19-9 levels over 37 U/ml were highly specific for accelerated disease progression after CRS/HIPEC. Lastly, there was no association between PFS and elevated CEA or CA 125. CONCLUSIONS: Elevated CA 19-9 is associated with decreased PFS in patients with CRPM. While traditionally CEA is the main tumor marker assessed in colon cancer, we found that CA 19-9 may better inform preoperative risk stratification for poor oncologic outcomes in patients with CRPM. However, prospective studies are required to confirm this association.

[Contribution of intraperitoneal chemotherapy in the treatment of colorectal peritoneal carcinoma. HIPEC, PIPAC, state of the art and future directions]. / La chimiothérapie intra-péritonéale dans le traitement de la carcinose péritonéale d'origine colorectale. CHIP, PIPAC, état des lieux et perspectives.

After more than a decade of good results using the combination of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal carcinosis of colorectal origin, the PRODIGE7 study, which specifically evaluated the role of HIPEC, failed to show any superiority in terms of overall and disease-free survival for the CRS+HIPEC combination compared with CRS alone. This study constituted a radical change in the knowledge and therapeutic attitudes observed to date. After reviewing the literature and the consensus of national and international experts, a synthesis is provided, together with an outlook on the questions raised and the therapeutic trials and innovations of the near future. An analysis of recent advances due to the advent of a new technique, PIPAC, is also proposed, as well as a review of current therapeutic trials in this field.

Is cytoreductive surgery and hyperthermic intraperitoneal chemotherapy still beneficial in patients diagnosed with colorectal peritoneal metastasis who underwent palliative chemotherapy?

BACKGROUND: With a 5-year overall survival of less than 5%, colorectal peritoneal metastasis (CPM) patients are often managed with palliative chemotherapy (CTx). In the past few decades, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been introduced as a possible curative treatment for highly selective CPM patients. We share our experience of CRS and HIPEC given the unique characteristics of the medical system and the benefit of CRS and HIPEC in palliative setting. METHODS: From April 2017 to October 2021, CPM patients who underwent CRS and HIPEC were analyzed. Patients were allocated into perioperative and palliative CTx arm based on the duration between initial diagnosis of CPM to undergoing CRS and HIPEC of 6 months. Data including perioperative parameters, postoperative outcomes, and survival were analyzed with a median follow-up of 28.5 months. RESULTS: Twenty-six CPM patients underwent CRS and HIPEC. Mean time from diagnosis of CPM to CRS and HIPEC was 5.5 months with 14 patients in the perioperative arm and 12 patients in the palliative arm. Perioperative group showed a longer RFS of 13.5 months compared to 8 months in the palliative group. Median overall survival of palliative group was 41.50 months, and 18 patients among all groups are alive at the time of this report. CONCLUSION: CRS and HIPEC could be a treatment option for a carefully selected CPM patients performed by experienced surgeons. Overall survival of 41.50 months in palliative group compared to 16.8 months from conventional systemic CTx supports CRS and HIPEC even in palliative patients.

Predictors of Financial Toxicity Risk Among Patients Undergoing Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC).

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is the preferred treatment for select patients with peritoneal malignancies. However, the procedure is resource intensive and costly. This study aimed to determine the risk of financial toxicity for patients undergoing CRS-HIPEC. PATIENTS AND METHODS: We performed a retrospective cohort study of patients undergoing CRS-HIPEC at a single institution from 2016 to 2022. We utilized insurance status, out-of-pocket expenditures, and estimated post-subsistence income to determine risk of financial toxicity. A multivariable logistic regression was used to determine risk factors for financial toxicity. RESULTS: Our final study cohort consisted of 163 patients. Average age was 58 [standard deviation 10] years, and 52.8% (n = 86) were male. A total of 52 patients (31.9%) were at risk of financial toxicity. A total of 36 patients (22.1%) were from the lower income quartiles (first or second) and 127 patients (77.9%) were from the higher income quartiles (third or fourth). A total of 47 patients (29%) were insured by Medicare, and 116 patients (71%) had private insurance. The median out-of-pocket expenditure across the study cohort was $3500, with a median of $5000 ($3341-$7350) for the at-risk group and $3341 ($2500-$4022) for the not at-risk group (p < 0.001). Risk factors for financial toxicity included high out-of-pocket expenditures and a lower income quartile. CONCLUSIONS: An estimated one-third of patients undergoing CRS-HIPEC at our institution were at risk for financial toxicity. Several preoperative factors were associated with an increased risk and could be utilized to identify patients who might benefit from interventions.

Distance Traveled and Disparities in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: The impact of distance traveled on cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) outcomes needs further investigation. METHODS: This retrospective study reviewed a prospectively managed single-center CRS/HIPEC 1992-2022 database. Zip codes were used to calculate distance traveled and to obtain data on income and education via census data. Patients were separated into three groups based on distance traveled in miles (local: ≤50 miles, regional: 51-99 miles, distant: ≥100 miles). Descriptive statistics, Kaplan-Meier method, and Cox regression were performed. RESULTS: The 1614 patients in the study traveled a median distance of 109.5 miles (interquartile range [IQR], 53.36-202.29 miles), with 23% traveling locally, 23.9% traveling regionally, and 53% traveling distantly. Those traveling distantly or regionally tended to be more white (distant: 87.8%, regional: 87.2%, local: 83.2%), affluent (distant: $61,944, regional: $65,014, local: $54,390), educated (% without high school diploma: distant: 10.6%, regional: 11.5%, local: 13.0%), less often uninsured (distant: 2.3%, regional: 4.6%, local: 5.2%) or with Medicaid (distant: 3.3%, regional: 1.3%, local: 9.7%). They more often had higher Peritoneal Carcinomatosis Index (PCI) scores (distant: 15.4, regional: 15.8, local: 12.7) and R2 resections (distant: 50.3%, regional: 52.2%, local: 40.5%). Median survival did not differ between the groups, and distance traveled was not a predictor of survival. CONCLUSION: More than 50% of the patients traveled farther than 100 miles for treatment. Although regionalization of CRS/HIPEC may be appropriate given the lack of survival difference based on distance traveled, those who traveled further had fewer health care disparities but higher PCI scores and more R2 resections, which raises concerns about access to care for the underserved, time to treatment, and surgical quality.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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 ≥ 60 years (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. CONCLUSIONS: 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.

The impact of the extent of surgery on late adverse effects following cytoreductive surgery and HIPEC.

AIM: To investigate the impact of the surgical extent on late adverse effects (LAE) following cytoreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC). METHOD: A prospective cohort study including patients undergoing CRS + HIPEC due to peritoneal metastases from gastrointestinal tumour origin. From 2006 through 2019, consecutive patients treated with CRS + HIPEC were followed at 3, 6 and 12 months, and LAEs were assessed using the symptom scales and items from the European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC QLQ-C30). Surgical extent was categorized into three groups (major, intermediate, minor) based on peritonectomy procedures and colorectal resections performed as part of CRS. EORTC data were analysed using a linear mixed effects regression model adjusted for age, gender, origin of tumour and comorbidity. RESULTS: In total, 257 patients who responded to at least one questionnaire during the follow-ups were included. Only diarrhoea symptoms were positively associated with surgical extent (mean differences: major vs. minor: 8.4 (-0.5; 17.2) (p = 0.06) and major vs. intermediate: 10.9 (3.8; 18.0) (p = 0.00)). Additionally, diarrhoea symptoms persisted throughout the study period and did not change over time (mean difference 12-3 months: -3.6 (-9.1; 1.7) (p-value = 0.18)). Overall, the levels of different symptom scales (fatigue, nausea and vomiting, pain, dyspnoea, and appetite loss) significantly decreased from 3 to 12 months. CONCLUSION: Patients undergoing extensive CRS suffer from persistent impaired gastrointestinal function in terms of diarrhoea compared patients undergoing to less extensive surgery. Attention should be directed at detecting such LAE and to guide patients accordingly.

Gastric cancer with peritoneal metastases: a single center outline and comparison of different surgical and intraperitoneal treatments.

INTRODUCTION: Gastric cancer with peritoneal metastasis (GCPM) has an unfavourable prognosis. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC) are promising treatment options that have been shown to improve survival. The aim of this study was to assess the impact of different treatments such as systemic chemotherapy, systemic chemotherapy + PIPAC, and CRS + HIPEC in patients with GCPM. MATERIAL AND METHODS: This single-centre retrospective study included 82 patients with GCPM treated between January 2016 and June 2021. After first-line chemotherapy, depending on disease response and burden, the patients were divided into three treatment groups: chemotherapy alone, chemotherapy + PIPAC, and CRS + HIPEC. The primary outcome was overall survival (OS) from diagnosis, which was compared among the treatment groups. RESULTS: Thirty-seven (45.1%) patients were administered systemic chemotherapy alone, 25 (30.4%) received chemotherapy + PIPAC, and 20 (24.4%) underwent CRS + HIPEC. The CRS + HIPEC group had better OS (median 24 months) than the PIPAC group (15 months, p = 0.01) and chemotherapy group (5 months, p = 0.0001). Following CRS + HIPEC, the postoperative grade 3-4 complication rate was 25%, and no postoperative in-hospital deaths occurred. The median disease-free survival (DFS) was 12 months. Multivariate analysis identified peritoneal carcinomatosis index (PCI) > 7 as an independent predictor of worse DFS. No independent predictors of OS were identified. CONCLUSION: Among patients with GCPM, we identified a highly selected population with oligometastatic disease. In this group, CRS + HIPEC provided a significant survival advantage with an acceptable major complication rate compared with other available therapies (systemic chemotherapy alone or in combination with PIPAC).

External validation of prognostic scores and comparison of predictive accuracy for patients with colorectal cancer with peritoneal metastases considered for cytoreductive surgery and intraperitoneal chemotherapy.

BACKGROUND AND OBJECTIVES: Prognostic scores are developed to facilitate the selection of patients with colorectal cancer peritoneal metastases (CRPM) for treatment with cytoreductive surgery (CRS) ± intraperitoneal chemotherapy (IPC). Three prominent prognostic scores are the Peritoneal Surface Disease Severity Score (PSDSS), the Colorectal Peritoneal Metastases Prognostic Surgical Score (COMPASS), and the modified COloREctal-Pc (mCOREP). We externally validate these scores and compare their predictive accuracy. METHODS: Data from consecutive CRPM patients who underwent CRS/IPC from 1996 to 2018 was used to externally validate COMPASS, PSDSS, and mCOREP. Analysis evaluated the efficacy of each score in predicting (1) open-close laparotomy-those found at laparotomy to not be eligible for curative intent CRS/IPC, (2) surgical futility-those who underwent open-close laparotomy, palliative debulking surgery, or had an overall survival of less than 12 months, and (3) overall and recurrence-free survival (OS, RFS). RESULTS: Prognostic scores were calculated for the 174-patient external validation cohort. COMPASS was most accurate in predicting open-close laparotomy, futile surgery, and survival (OS and RFS). Area under the curve (AUC) for open-close prediction was 0.78 (95% confidence interval, CI: 0.68-0.87), representing useful discrimination. However, AUC for futility prediction was 0.62 (95% CI: 0.52-0.71), and C-statistic for OS was 0.65 indicating only possibly helpful discrimination. C-statistic for RFS was 0.59 indicating poor discrimination. CONCLUSION: While COMPASS showed the best statistical behavior, accuracy for several clinically relevant outcomes remains low, and thus applicability to clinical practice limited.

Risk factors for gastrointestinal perforation and anastomotic leak in patients submitted to cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

BACKGROUND: Gastrointestinal leak is one of the most feared complications after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) and harbors significant postoperative morbidity and mortality. We aim to identify risk-factors for anastomotic leak (AL) and gastrointestinal perforation (GP) to optimize postoperative outcomes of this population. METHODS: We performed a retrospective analysis of 1043 consecutive patients submitted to CRS in a single institution. Potential risk factors for AL and GP, both related to patient overall condition, disease status and surgical technique were reviewed. RESULTS: Anastomotic leaks were identified in 5.2% of patients, and GPs in 7.0%. The independent risk-factors for AL were age at surgery (OR1.40; CI95% 1.10-1.79); peritoneal cancer index (PCI) (OR1.04, CI95% 1.01-1.07); Cisplatin dose >240 mg during HIPEC (OR3.53; CI95% 1.47-8.56) and the presence of colorectal (CR) or colo-colic (CC) anastomosis (OR5.09; CI95% 2.71-9.53, and 4.58; CI95% 1.22-17.24 respectively). Male gender and intraoperative red blood cell transfusions were the only independent risk factors for GP identified (OR1.70; CI95% 1.04-2.78 and 1.06; CI95% 1.01-1.12, respectively). Regarding 30-day and 90-day postoperative mortality, independent risk-factors were mainly related to patient's overall condition. CONCLUSION: Gastrointestinal leaks are a frequent source of postoperative morbidity, mainly at the expense of GP. A careful and systematic intraoperative revision of all potential gastrointestinal injuries is equally critical to perfecting anastomotic fashioning techniques to decrease gastrointestinal complication rates. We identified multiple risk-factors for AL and GP related to disease status and patient condition. Our study suggests that patient-related conditions are of paramount relevance, highlighting the importance of patient selection and preoperative patient optimization.

Immune profile of patients with peritoneal carcinomatosis selected for CRS-HIPEC therapy.

Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment option for peritoneal carcinomatosis (PC) from colorectal cancer (CRC), which is otherwise a terminal stage of disease. Nevertheless, survival outcomes are only marginally superior to other treatments. This fact highlights the need for better strategies to control intra-abdominal disease recurrence after CRS-HIPEC, including the complementary use of immunotherapies. The aim of this study was therefore to investigate the immune phenotype of T cells in patients with PC. Fifty three patients with CRC (34 patients with PC and 19 patients without PC) were enrolled in a prospective study (clinicaltrials.gov: NCT04108936). Peripheral blood and omental fat were collected to isolate peripheral blood mononuclear cells (PBMCs) and adipose tissue mononuclear cells (ATMCs). These cells were analysed by flow cytometry using a panel focused upon T cell memory differentiation and exhaustion markers. We found a more naïve profile for CD8+ T cells in peripheral blood and intra-abdominal fat of PC patients compared to comparator group (CG) patients. Furthermore, there was an over-representation of CD4+ T cells expressing inhibitory receptors in adipose tissue of PC patients, but not in blood. Our description of intraperitoneal T cell subsets gives us a better understanding of how peritoneal carcinomatosis shapes local immune responses.

Application of HIPEC simulations for optimizing treatment delivery strategies.

INTRODUCTION: Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) aims to treat microscopic disease left after CytoReductive Surgery (CRS). Thermal enhancement depends on the temperatures achieved. Since the location of microscopic disease is unknown, a homogeneous treatment is required to completely eradicate the disease while limiting side effects. To ensure homogeneous delivery, treatment planning software has been developed. This study compares simulation results with clinical data and evaluates the impact of nine treatment strategies on thermal and drug distributions. METHODS: For comparison with clinical data, three treatment strategies were simulated with different flow rates (1600-1800mL/min) and inflow temperatures (41.6-43.6 °C). Six additional treatment strategies were simulated, varying the number of inflow catheters, flow direction, and using step-up and step-down heating strategies. Thermal homogeneity and the risk of thermal injury were evaluated. RESULTS: Simulated temperature distributions, core body temperatures, and systemic chemotherapeutic concentrations compared well with literature values. Treatment strategy was found to have a strong influence on the distributions. Additional inflow catheters could improve thermal distributions, provided flow rates are kept sufficiently high (>500 mL/min) for each catheter. High flow rates (1800 mL/min) combined with high inflow temperatures (43.6 °C) could lead to thermal damage, with CEM4310 values of up to 27 min. Step-up and step-down heating strategies allow for high temperatures with reduced risk of thermal damage. CONCLUSION: The planning software provides valuable insight into the effects of different treatment strategies on peritoneal distributions. These strategies are designed to provide homogeneous treatment delivery while limiting thermal injury to normal tissue, thereby optimizing the effectiveness of HIPEC.

[Establishment of treatment center for peritoneal metastasis in colorectal cancer].

The prognosis of patients with peritoneal metastasis from colorectal cancer is poor. At present, the comprehensive treatment system based on cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has significantly improved the survival of these patients. However, CRS and HIPEC have strict indications, high procedural difficulty, and high morbidity and mortality. If CRS+HIPEC is performed in an inexperienced center, overall survival and quality of life of patients may bo compromised. The establishment of specialized diagnosis and treatment centers can provide a guarantee for standardized clinical diagnosis and treatment. In this review, we first introduced the necessity of establishing a colorectal cancer peritoneal metastasis treatment center and the construction situation of the diagnosis and treatment center for peritoneal surface malignancies at home and abroad. Then we focused on introducing our construction experience of the colorectal peritoneal metastasis treatment center, and emphasized that the construction of the center must be done well in two aspects: firstly, the clinical optimization should be realized and the specialization of the whole workflow should be strengthened; secondly, we should ensure the quality of patient care and the rights, well-being and health of every patient.

Role of Tumor-informed Personalized Circulating Tumor DNA Assay in Informing Recurrence in Patients With Peritoneal Metastases From Colorectal and High-grade Appendix Cancer Undergoing Curative-intent Surgery.

OBJECTIVE: To investigate the role of a personalized, tumor-informed circulating tumor DNA (ctDNA) assay in informing recurrence in patients with peritoneal metastases (PM) from colorectal (CRC) and high-grade appendix (HGA) cancer after curative cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). BACKGROUND: Over 50% of patients with CRC/HGA-PM recur after optimal CRS-HIPEC. The limited sensitivity of axial imaging and diagnostic biomarkers is a significant cause of delay in the detection of recurrence and initiation of further therapies. Plasma ctDNA has a promising role in monitoring response to treatment and/or recurrence after primary cancer resection. METHODS: Patients with CRC/HGA-PM who underwent curative CRS-HIPEC and serial postresection ctDNA assessments were included. Patients with rising postoperative ctDNA levels were compared with those with stable, undetectable ctDNA levels. Primary outcomes were the percentage of patients with recurrence and disease-free survival (DFS). Secondary outcomes were overall survival, ctDNA sensitivity, lead time, and performance of ctDNA compared with carcinoembryonic antigen. RESULTS: One hundred thirty serial postresection ctDNA assessments [median 4, interquartile range (IQR), 3 to 5] were performed in 33 patients (n = 13 CRC, n = 20 HGA) who underwent completeness of cytoreduction-0/1 CRS with a median follow-up of 13 months. Of the 19 patients with rising ctDNA levels, 90% recurred versus 21% in the stable ctDNA group (n = 14, < 0.001). Median DFS in the rising ctDNA cohort was 11 months (IQR, 6 to 12) and not reached in the stable ( P = 0.01). A rising ctDNA level was the most significant factor associated with DFS (hazard ratio: 3.67, 95% CI: 1.06-12.66, P = 0.03). The sensitivity and specificity of rising ctDNA levels in predicting recurrence were 85% and 84.6%, respectively. The median ctDNA lead time was 3 months (IQR, 1 to 4). Carcinoembryonic antigen was less sensitive (50%) than ctDNA. CONCLUSIONS: This study supports the clinical validity of serial ctDNA assessment as a strong prognostic biomarker in informing recurrence in patients with CRC/HGA-PM undergoing curative resection. It also holds promises for informing future clinical trial designs and further research.

[Preoperative Prognostic Factors in CRS plus HIPEC for Patients with Peritoneal Dissemination of Colorectal Cancer].

Peritoneal dissemination of colorectal cancer has the poorest prognosis among metastatic sites, with an average overall survival of less than 6 months. Various treatment methods have been reported for these patients, and recently there have been several reports showing the usefulness of cytoreductive surgery(CRS)combined with hyperthermic intraperitoneal chemotherapy (HIPEC). However, the studies on this treatment are limited. In this study, we retrospectively reviewed cases of CRS plus HIPEC. Twenty-one patients who underwent CRS plus HIPEC at Tokyo Medical University Hospital and Toda Central General Hospital between August 2014 and December 2017 were included in this study. The long-term and short-term survival groups were analyzed separately, and predictors of preoperative treatment efficacy were examined. The surgical approach was open in 16 cases and laparoscopic in 5 cases. Complete resection was achieved in 10 of these patients. Postoperative complications occurred in 6 patients. There were no deaths within 90 days of surgery. The median overall survival was 17.0 months, and the 1-year survival rate was 65%. Median progression-free survival was 11.0 months. In a multivariate analysis predicting long-term versus short-term survival groups, sex, primary tumor location, and P factor were independent predictors of treatment response. CRS plus HIPEC therapy is considered an effective treatment option. The predictors of preoperative treatment response include sex, primary tumor location, and P factor.

Long-Term Survival in Patients Treated with Cytoreduction and Heated Intraperitoneal Chemotherapy for Peritoneal Mesothelioma at a Single High-Volume Center.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare diagnosis with a dismal prognosis if untreated. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is shown to significantly improve survival. Our institution is uniquely positioned to report long-term outcomes in MPM with CRS-HIPEC, due to our robust peritoneal surface disease program existing over the past three decades. METHODS: Our prospectively maintained, single-institution database of CRS-HIPEC cases was reviewed, identifying 111 consecutive patients with MPM over 28 years (1993-2021). Prognostic, operative, and pathologic factors were reviewed. Overall survival (OS) and conditional survival (CS) analyses were performed. RESULTS: The average age was 55.1 years; 58.6% of patients were male; 17 of 111 patients (15.3%) had a second CRS-HIPEC. At first CRS-HIPEC, the average PCI score was 18.7, and the perfusate drugs were platinum-based (72.1%) and mitomycin C (27.9%). The resection status at first CRS-HIPEC was R2a (46.4%), followed by R0-1 (29.1%), and R2b-c (24.5%). Median OS was 3.3 years for the entire cohort, with 75th and 25th percentiles at 10.7 months and 10.6 years. Median CS was improved if patients survived to the 1-year postoperative mark (4.9 years, p < 0.01) and trended toward further improvement with each passing year. If 3-year postoperative survival was achieved, the median CS improved to 6.1 years. CONCLUSIONS: This represents one of the largest and lengthiest, single-center, longitudinal, case series of peritoneal mesothelioma treated with CRS-HIPEC. The OS suggests efficacy for CRS-HIPEC for MPM. Long-term survival improves significantly after patients achieve the 1-year, postoperative mark.

Neoadjuvant Chemotherapy Followed by Cytoreductive Surgery and HIPEC Improves Survival in Peritoneal Metastatic Gastric Cancer.

INTRODUCTION: This study examined the difference in overall survival (OS) between peritoneal metastatic gastric cancer (PMGC) patients who underwent neoadjuvant chemotherapy followed by cytoreductive surgery ± hyperthermic intraperitoneal chemotherapy (CRS ± HIPEC) and those who did not have surgery but instead received palliative chemotherapy. METHODS: This retrospective study included 80 patients who were followed up with the diagnosis of PMGC, those undergoing neoadjuvant chemotherapy followed by CRS ± HIPEC (CRS ± HIPEC group) and those receiving chemotherapy only (non-surgical group), in the medical oncology clinic between April 2011 and December 2021. Clinicopathological features, treatments, and OS of the patients were compared. RESULTS: There were 32 patients in the SRC CRS ± HIPEC group and 48 in the non-surgical group. In the CRS ± HIPEC group, CRS + HIPEC was performed on 20 patients, and only CRS was performed on 12 patients. All of the patients who underwent CRS + HIPEC, and 5 of the patients who underwent only CRS received neoadjuvant chemotherapy. While the median OS was 19.7 (15.5-23.8) months in the CRS ± HIPEC group, the median OS was 6.8 (3.5-10.2) months in the non-surgical group (p < 0.001). CONCLUSION: As a result, CRS + HIPEC significantly improves survival in PMGC patients. With experienced surgical centres and appropriate patient selection, the life expectancy of patients with PM can be extended.

Closed hyperthermic intraperitoneal chemotherapy with CO2 recirculation system compared with the open Coliseum technique in peritoneal malignity treatment.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis can be performed in two ways: first, the standard open abdominal technique (Open HIPEC); or second, the closed technique. In recent years, a new technique has been introduced to perform closed HIPEC; the Peritoneal Recirculation System (PRS-1.0 Combat) with CO2 recirculation technology (PRS Closed HIPEC). The objective of this study is to present our experience with the PRS Closed HIPEC by comparing the intraoperative, postoperative and oncological results with the standard Open HIPEC technique (the Coliseum technique). METHODS: Data on patients undergoing CRS and HIPEC at the Sanchinarro University Hospital, Madrid from October 2012 to June 2021 were collected in a prospective database. The inclusion criteria were patients with primary or recurrent peritoneal metastases in gastrointestinal malignancies or ovarian cancer. The presence of an unresectable peritoneal carcinomatosis, the coexistence of another oncological disease, unresectable and distant metastases were the exclusion criteria. RESULTS: From October 2014 to June 2021, 84 patients underwent CRS and HIPEC at the Sanchinarro University Hospital, Madrid with curative intent. Since the introduction of the PRS Closed HIPEC technique in 2016, 65 patients have been treated. Before the introduction of PRS Closed HIPEC, 19 cases were performed using the Coliseum technique (the Open HIPEC group). The intraoperative results were similar in the two groups. Complete cytoreduction was achieved in all cases in the Open HIPEC group and in 98% in the PRS Closed HIPEC group. The rate of major complications was similar between the groups. Median Overall Survival (OS) resulted better in the Closed HIPEC group (67 months) with respecto to the Open group (43 months) (p < 0,001). Median Disease-Free Survival (DFS) was 15 months in the Open HIPEC group and 40 months in the PRS Closed HIPEC group (p < 0.001). CONCLUSION: The Peritoneal Recirculation System with CO2 recirculation technology (PRS Closed HIPEC) is a reproducible and safe technique and may represent a valid alternative for the administration of HIPEC.