Decision Regret in Patients with Appendiceal Cancer Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Decision regret is an emerging patient reported outcome. The aim of this study was to assess the incidence of regret in patients with appendiceal cancer (AC) who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). PATIENTS AND METHODS: An anonymous survey was distributed to patients through the Appendix Cancer and Pseudomyxoma Peritonei (ACPMP) Research Foundation. The Decision Regret Scale (DRS) was employed, with DRS > 25 signifying regret. Patient demographics, tumor characteristics, postoperative outcomes, symptoms (FACT-C), and PROMIS-29 quality of life (QoL) scores were compared between patients who regretted or did not regret (NO-REG) the procedure. RESULTS: A total of 122 patients were analyzed. The vast majority had no regret about undergoing CRS-HIPEC (85.2%); 18 patients expressed regret (14.8%). Patients with higher regret had: income ≤ $74,062 (72.2% vs 44.2% NO-REG; p = 0.028), major complications within 30 days of surgery (55.6% vs 15.4% NO-REG; p < 0.001), > 30 days hospital stay (38.9% vs 4.8% NO-REG; p < 0.001), a new ostomy (27.8% vs 7.7% NO-REG; p = 0.03), >1 CRS-HIPEC procedure (56.3% vs 12.6% NO-REG; p < 0.001). Patients with worse FACT-C scores had more regret (p < 0.001). PROMIS-29 QOL scores were universally worse in patients with regret. Multivariable analysis demonstrated > 30 days in the hospital, new ostomy and worse gastrointestinal symptom scores were significantly associated with regret. CONCLUSIONS: The majority of patients with AC undergoing CRS-HIPEC do not regret undergoing the procedure. Lower income, postoperative complications, an ostomy, undergoing > 1 procedure, and with worse long-term gastrointestinal symptoms were associated with increased regret. Targeted perioperative psychological support and symptom management may assist to ameliorate regret.

Systematic Cholecystectomy During Cytoreductive Surgery Plus HIPEC: A Critical Analysis of an Empirical Tradition.

BACKGROUND: Some procedures performed during cytoreductive surgery (CRS) and hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) are based on empirical data. One of these procedures is systematic cholecystectomy. This study aimed to perform a critical analysis of the need for systematic cholecystectomy during CRS+HIPEC of patients with peritoneal carcinomatosis using long-term follow-up data. METHODS: Patients with peritoneal surface malignancies who were candidates for CRS+HIPEC and underwent surgery between January 2008 and December 2022 were analyzed. For patients with gallbladder involvement due to the disease or for patients whose preoperative study showed the presence of cholelithiasis, cholecystectomy was performed as part of the surgery, which was avoided for the remaining patients. All postoperative adverse events that occurred in the first 90 days were recorded, and clinical records focused on the development of biliary pathology during the follow-up period were studied. RESULTS: The results from a consecutive series of 443 patients with peritoneal surface malignancies who underwent surgery between January 2008 and December 2022 were analyzed. The average age of the cohort was 50 years. The median follow-up period for the cohort was 41 months (range, 12-180 months), with a disease-free survival of 17 months. For 373 of the patients, CRS+HIPEC was completed without an associated cholecystectomy, and in 16 of them, the appearance of cholelithiasis was detected during the follow-up period. Only two patients in the series showed complications derived from gallstones and required a delayed cholecystectomy. CONCLUSIONS: Although cholecystectomy is a safe procedure in the context of CRS+HIPEC, it is not risk free, and its routine performance may be unnecessary.

Comparison of EPIC Versus HIPEC in the Treatment of Colorectal Peritoneal Metastases and Appendix Tumors Using Inverse Probability of Treatment Weighting.

BACKGROUND: The selection of hyperthermic intraperitoneal chemotherapy (HIPEC) or early postoperative intraperitoneal chemotherapy (EPIC) for peritoneal metastases from colorectal cancer or appendiceal neoplasms following cytoreductive surgery (CRS) depends on the surgeon's discretion. This study was designed to compare postoperative and oncologic outcomes of HIPEC and EPIC using inverse probability of treatment weighting (IPTW). METHODS: This study included 175 patients who received HIPEC or EPIC following CRS at a single tertiary university hospital between December 1999 and December 2020. Inverse probability of treatment weighting analysis was performed to control for pretreatment characteristics between the two groups. Multivariate analysis was performed to determine factors associated with postoperative and survival outcomes. RESULTS: After IPTW, no significant differences in baseline demographics and tumor characteristics were observed between the two groups. The HIPEC group had a significantly longer operation time than the EPIC group. The EPIC group showed a significantly higher postoperative mortality rate than the HIPEC group. Operation time (odds ratio [OR] 1.01; 95% confidence interval [CI] 1.01-1.02; p < 0.001), bowel anastomosis (OR 7.25; 95% CI 1.16-45.2; p = 0.034), neoadjuvant chemotherapy (OR 7.62; 95% CI 1.85-31.4; p = 0.005), and EPIC (OR 8.76; 95% CI 2.16-35.5; p = 0.002) were independent risk factors for major surgical complications. No association was observed between intraperitoneal chemotherapy type and major hematologic toxicity, overall survival, progression-free survival, or peritoneal progression-free survival. CONCLUSIONS: EPIC was a risk factor for major surgical complications. Survival outcomes were similar between the two types of intraperitoneal chemotherapy.

A phase Ib randomized multicenter trial of isolated hepatic perfusion in combination with ipilimumab and nivolumab for uveal melanoma metastases (SCANDIUM II trial).

BACKGROUND: Uveal melanoma (UM) is a rare malignancy where 50% of patients develop metastatic disease primarily affecting the liver. Approximately 40% of patients with metastatic UM respond to one-time isolated hepatic perfusion (IHP) with high-dose melphalan. This phase I trial investigates the safety and clinical efficacy of IHP combined with ipilimumab (IPI) and nivolumab (NIVO). PATIENTS AND METHODS: Immunotherapy-naïve patients were randomized in this phase I trial to receive either IHP followed by IPI 3 mg/kg and NIVO 1 mg/kg (IPI3/NIVO1) for four cycles (post-operative arm), or one cycle of preoperative IPI3/NIVO1, IHP and then three cycles of IPI3/NIVO1 (pre-post-operative arm), followed by maintenance therapy with NIVO 480 mg for 1 year. RESULTS: Eighteen patients were enrolled and randomized. Three patients did not undergo IHP as planned. In total, 11/18 patients (6 in the post-operative arm and 5 in the pre-post-operative arm) did not complete the planned four cycles of IPI3/NIVO1. Toxicity to IHP was similar in both groups, but the number of immune-related adverse events (AEs) was higher in the pre-post-operative arm. Among assessable patients, overall response rate was 57% in the post-operative arm (4/7) and 22% in the pre-post-operative arm (2/9). CONCLUSIONS: Combination therapy with IHP and IPI3/NIVO1 was associated with severe AEs. The efficacy of this combination is encouraging with high response rates. One cycle of preoperative IPI/NIVO before IHP did not show potential benefits in terms of safety or efficacy.

Efficacy and safety of intrapleural perfusion with hyperthermic chemotherapy for malignant pleural effusion: a meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of intrapleural perfusion with hyperthermic chemotherapy (IPHC) in treating malignant pleural effusion (MPE). METHODS: PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), VIP Chinese Science and Technology Journal Full-text Database (VP-CSJFD), and Wanfang database were searched by computer from database establishment to January 17, 2024. Relevant randomized controlled articles with IPHC as the observational group and intrapleural perfusion chemotherapy (IPC) as the control group for MPE were included. Then, the methodological quality of the included articles was evaluated and statistically analyzed using Stata 16.0. RESULTS: Sixteen trials with 647 patients receiving IPHC and 661 patients receiving IPC were included. The meta-analysis found that MPE patients in the IPHC group had a more significant objective response rate [RR = 1.31, 95%CI (1.23, 1.38), P < 0.05] and life quality improvement rate [RR = 2.88, 95%CI (1.95, 4.24), P < 0.05] than those in the IPC group. IPHC and IPC for MPE patients had similar incidence rates of asthenia, thrombocytopenia, hepatic impairment, and leukopenia. CONCLUSION: Compared with IPC, IPHC has a higher objective response rate without significantly increasing adverse reactions. Therefore, IPHC is effective and safe. However, this study is limited by the quality of the literature. Therefore, more high-quality, multi-center, large-sample, rigorously designed randomized controlled clinical studies are still needed for verification and evaluation.

Adoption of an Enhanced Recovery After Surgery Protocol Increases Cost of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy and Does not Improve Outcomes.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols have been shown to reduce length of stay (LOS) and complications. The impact of ERAS protocols on the cost of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has not been studied. PATIENTS AND METHODS: We performed a retrospective cohort analysis of patients undergoing CRS-HIPEC from 2016-2022 at a single quaternary center. Propensity score matching was used to create pre-and post-ERAS cohorts. Cost, overall and serious complications, and intensive care unit (ICU) length of stay (LOS) between the two cohorts were compared using the Mann-Whitney U-test for continuous variables and χ2 test for categorical variables. RESULTS: Our final matched cohort consisted of 100 patients, with 50 patients in both the pre- and post-ERAS groups. After adjusting for patient complexity and inflation, the median total cost [$75,932 ($67,166-102,645) versus $92,992 ($80,720-116,710), p = 0.02] and operating room cost [$26,817 ($23,378-33,121) versus $34,434 ($28,085-$41,379), p < 0.001] were significantly higher in the post-ERAS cohort. Overall morbidity (n = 22, 44% versus n = 17, 34%, p = 0.40) and ICU length of stay [2 days (IQR 1-3) versus 2 days (IQR 1-4), p = 0.70] were similar between the two cohorts. A total cost increase of $22,393 [SE $13,047, 95% CI (-$3178 to $47,965), p = 0.086] was estimated after implementation of ERAS, with operating room cost significantly contributing to this increase [$8419, SE $1628, 95% CI ($5228-11,609), p < 0.001]. CONCLUSIONS: CRS-HIPEC ERAS protocols were associated with higher total costs due to increased operating room costs at a single institution. There was no significant difference in ICU LOS and complications after the implementation of the ERAS protocol.

Liver Resection Under Total Hepatic Vascular Exclusion with In Situ Hypothermic Isolated Hepatic Perfusion for Advanced Liver Tumors.

PURPOSE: Continuous dissection or simultaneous reconstruction of the hepatic vein (HV) and inferior vena cava (IVC) was achieved under total hepatic vascular exclusion (THVE) with in situ hypothermic isolated hepatic perfusion (HIHP) in two cases. CASE 1: The patient previously underwent liver resections with the right HV for colorectal liver metastasis (CRLM). This time, the CRLM had invaded the left HV and IVC, and five courses of FOLFILI plus ramucirumab were given, resulting in stable disease. Due to expected high HV pressure, liver parenchymal transection was started under THVE. Sub-segmentectomy with patch graft plasty of the IVC and reconstruction of the left HV using a jugular vein graft were performed under THVE and HIHP. This patient died at home 3 months after surgery; the cause of death was unknown. CASE 2: Hepatocellular carcinoma in the caudate lobe was in extensive contact with the roots of three main HVs and the IVC, and pressed the hepatocaval confluence, with high HV pressure expected. In addition, tumor thrombosis extended to both the main portal vein and the common bile duct, resulting in the inability to introduce chemotherapy. After tumor thrombectomy, liver parenchymal transection was started under THVE. Extended left hepatectomy with wedge resection, and primary suture of the right HV and IVC was performed under THVE and HIHP. Recurrence-free and overall survivals were 8 months (lung metastasis) and 31 months, respectively. CONCLUSIONS: In liver resection for liver tumors located in the hepatocaval confluence, THVE with HIHP is useful for ensuring the safety.

Anastomotic leakage following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal cancer: A clinical cohort study.

BACKGROUND: Extended oncological resections for colorectal cancer surgery are associated with a high rate of complications, especially anastomotic leakage (AL). This study determines the incidence of risk factors for postoperative complications following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal cancer (CRC). METHODS: In this cohort study, the clinical data of all patients with CRC, treated with CRS and HIPEC, from 2011 to 2021 was analyzed. We considered patients' characteristics, tumor-specific features, postoperative complications, and hospital stay using Chi-Square-test or Fisher's exact test. The Mann-Whitney-U-test was used to measure the probability of differences between two sets of data. RESULTS: Of 1089 HIPEC procedures performed in the study center, 185 patients with CRC and peritoneal metastasis were treated with CRS and HIPEC after formation of at least one anastomosis and therefore included in this study. This included synchronous and metachronous peritoneal metastasis with a mean peritoneal cancer index of 8.67 ± 5.22. In this cohort, AL occurred in 12 (6.5 %) patients. There was no correlation between the number of anastomoses and the occurrence of an AL (p = 0.401). CONCLUSION: This study reports a low risk of AL after CRS with HIPEC for CRC, comparable to other published data. If a complete cytoreduction seems possible, the risk of anastomotic leakage should not negatively influence the decision to resect. Further studies on this subject are essential to validate our findings.

Quality of Life Analysis of Patients Treated with Percutaneous Hepatic Perfusion for Uveal Melanoma Liver Metastases.

PURPOSE: Percutaneous hepatic perfusion with melphalan (M-PHP) is a minimally invasive therapy with proven efficacy in patients with uveal melanoma (UM) liver metastases. M-PHP is associated with a short hospital admission time and limited systemic side effects. In this study, we assessed quality of life (QoL) in UM patients treated with M-PHP. MATERIALS AND METHODS: A prospective, single-center study including 24 patients treated with M-PHP for UM metastases to the liver. QoL questionnaires were collected at baseline, on day 2/3 after M-PHP, and on day 7 and day 21 after M-PHP, according to study protocol. The results were scored according to EORTC-QLQ C30 global health status (GHS), functional scales, and symptom scales. The difference in scores at baseline and subsequent time points was analyzed with the Wilcoxon signed-rank test and multiple testing Bonferroni correction. Adverse events (AE) were registered up to 30 days after M-PHP according to CTCAE v5.0. RESULTS: Twenty-four patients (14 males; median age 63.0 years) completed 96 questionnaires. Most scores on all scales declined on day 2/3 after M-PHP. On day 21 after M-PHP, 12 out of 15 scores returned to baseline, including median GHS scores. Three variables were significantly worse on day 21 compared to baseline: fatigue (6-33; p = 0.002), physical functioning (100 vs 86.7; p = 0.003), and role functioning (100 vs 66.7; p = 0.001). Grade 3/4 AEs consisted mainly of hematological complications, such as leukopenia and thrombopenia. CONCLUSION: M-PHP causes fatigue and a decline in physical and role functioning in the 1st weeks after treatment, but GHS returns to baseline levels within 21 days. LEVEL OF EVIDENCE 3: Cohort study.

Troponin Elevation in Patients Undergoing Percutaneous Hepatic Perfusion for Metastatic Uveal Melanoma.

BACKGROUND: Percutaneous Hepatic Perfusion (PHP) is a liver directed regional therapy recently FDA approved for metastatic uveal melanoma to the liver involving percutaneous isolation of liver, saturation of the entire liver with high-dose chemotherapy and filtration extracorporeally though in line filters and veno-venous bypass. The procedure is associated with hemodynamic shifts requiring hemodynamic support and blood product resuscitation due to coagulopathy. OBJECTIVE: To assess the cardiac safety and subsequent clinically significant sequalae of this therapy. METHODS: Consecutive PHP procedures done at our center between 2010-2022 were assessed retrospectively. Cardiac risk factors, post procedural cardiac enzymes, electrocardiograms, and transthoracic echocardiograms along with 90-day cardiac outcomes were reviewed. All data were reviewed by cardio-oncologists at our institution. RESULTS: Of 37 patients reviewed, mean age was 63 years and 57% were women. 132 procedures were performed with an average of 3.57 procedures per patient. 68.6% of patients had elevated troponin during at least 1 procedure. No patients were found to have acute coronary syndrome, heart failure, unstable arrhythmias, or cardiac death. No patients had notable echocardiographic changes. 10.8% of patients with positive troponin had asymptomatic transient electrocardiographic changes not meeting criteria for myocardial infarction. One patient had non-sustained ventricular tachycardiac intra-operatively which did not recur subsequently. Three patients died from non-cardiac causes within 90-days. There was no oncology treatment interruption, even in those with troponin elevation. In multivariable analysis, a history of hyperlipidemia was a predictor of postoperative troponin elevation. (P = .042). CONCLUSION: Percutaneous Hepatic Perfusion is safe and associated with a transient, asymptomatic troponin elevation peri-operatively without major adverse cardiac events at 90 days. The observed troponin elevation is likely secondary to coronary demand-supply mismatch related to procedural hemodynamic shifts, hypotension, and anemia.

Percutaneous hepatic perfusion using melphalan in patients with uveal melanoma and liver metastases carries no significant cardiac adverse events.

Technical considerations for isolated limb perfusion: A consensus paper.

BACKGROUND: Isolated limb perfusion (ILP) is a well-established surgical procedure for the administration of high dose chemotherapy to a limb for the treatment of advanced extremity malignancy. Although the technique of ILP was first described over 60 years ago, ILP is utilised in relatively few specialist centres, co-located with tertiary or quaternary cancer centres. The combination of high dose cytotoxic chemotherapy and the cytokine tumour necrosis factor alpha (TNFα), mandates leakage monitoring to prevent potentially serious systemic toxicity. Since the procedure is performed at relatively few specialist centres, an ILP working group was formed with the aim of producing technical consensus guidelines for the procedure to streamline practice and to provide guidance for new centres commencing the technique. METHODS: Between October 2021 and October 2023 a series of face to face online and hybrid meetings were held in which a modified Delphi process was used to develop a unified consensus document. After each meeting the document was modified and recirculated and then rediscussed at subsequent meeting until a greater than 90% consensus was achieved in all recommendations. RESULTS: The completed consensus document comprised 23 topics in which greater than 90% consensus was achieved, with 83% of recommendations having 100% consensus across all members of the working group. The consensus recommendations covered all areas of the surgical procedure including pre-operative assessment, drug dosing and administration, perfusion parameters, hyperthermia, leakage monitoring and theatre logistics, practical surgical strategies and also post-operative care, response evaluation and staff training. CONCLUSION: We present the first joint expert-based consensus statement with respect to the technical aspects of ILP that can serve as a reference point for both existing and new centres in providing ILP.

The effect of a single dose of nivolumab prior to isolated limb perfusion for patients with in-transit melanoma metastases: An interim analysis of a phase Ib/II randomized double-blind placebo-controlled trial (NivoILP trial).

OBJECTIVE: ILP has shown to achieve high response rates in patients with melanoma ITM. Possibly there is a synergistic mechanism of action of ILP and anti-PD1. The aim of this trial was to investigate the safety and efficacy of adding a single dose of systemic anti-PD1 to isolated limb perfusion (ILP) for patients with melanoma in-transit metastases (ITM). METHODS: In this placebo controlled double-blind phase Ib/II trial, patients with melanoma ITM were randomized 1:1 to either a single systemic dose of nivolumab or placebo one day prior to ILP. The primary endpoint was complete response (CR) rate at three months, and safety in terms of incidence and severity of adverse events (AEs). RESULTS: A total of 20 patients were included. AEs of any grade occurred in 90% of patients in the nivolumab arm and in 80% in the placebo arm within three months after ILP. Grade 3 AEs were reported in 40% and 30% respectively, most commonly related to wound infection, wound dehiscence, or skin necrosis. There were no grade 4 or 5 AEs reported. The CR rate was 75% in the nivolumab arm and 60% in the placebo arm. The 1-year local progression-free rate was 86% in the nivolumab arm and 67% in the placebo arm. The 1-year OS was 100% in both arms. CONCLUSION: For patients with melanoma ITM, the addition of a single systemic dose of nivolumab the day before ILP is considered safe and feasible with promising efficacy. Accrual will continue in a phase 2 trial.

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.

Feasibility and efficacy of indocyanine green in monitoring systemic drug leakage during isolated limb perfusion for recurrent melanoma of extremity.

Melanoma is known for its high metastatic potential and aggressive growth. Recurrence is common post-surgery, sometimes leading to unresectable disease. Locally recurrent unresectable melanoma of extremity has been treated with high-dose anticancer chemotherapy via isolated limb perfusion (ILP) to improve local efficacy of drug and salvage limbs. Standard ILP monitoring uses radiolabeled dyes, requiring specialized personnel and involving radiation exposure. In this case, we used indocyanine green (ICG) to track systemic drug leakage during ILP. A 47-year-old gentleman with recurrent malignant melanoma of the left foot, operated twice earlier and treated with adjuvant pembrolizumab, presented with multiple in-transit metastases in the limb. ILP was planned, with 5 mg ICG administered in the perfusion solution along with high-dose melphalan. Stryker's SPI PHI handheld device was employed to visualize ICG during ILP. Absence of fluorescence beyond the involved extremity, such as fingers, ears, and the abdominal wall, indicated no systemic drug dispersion. For control, technetium radiocolloid dye was co-administered, monitored by a precordial gamma probe, confirming no systemic leakage, and validating effectiveness of ICG in leakage monitoring. ICG proves to be a safe, reliable, cost-effective, radiation-free approach for precise systemic drug leakage monitoring during ILP for recurrent melanoma of extremity.

Initial Experience Using Laparoscopic HIPEC for Gastric Cancer with Peritoneal Metastasis: Safety and Outcomes.

BACKGROUND: Peritoneal metastases (PM) develop in approximately 20% of patients with gastric cancer (GC). For selected patients, treatment of PM with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results. This report aims to describe the safety and perioperative outcomes of laparoscopic HIPEC for GC/PM. METHODS: This retrospective cohort study evaluated patients who had GC and PM treated with laparoscopic HIPEC (2018-2022). The HIPEC involved cisplatin and mitomycin C (MMC) or MMC alone. The primary end point was perioperative safety. RESULTS: The 22 patients in this study underwent 27 procedures. The mean age was 58 ± 13 years. All the patients were Eastern Cooperative Oncology Group (ECOG) 0 or 1 (55 and 45%, respectively). Five patients underwent a second laparoscopic HIPEC, with a median of 126 days (interquartile range [IQR], 117-166 days) between procedures. The median peritoneal carcinomatosis index (PCI) was 4 (IQR, 2-9), and the median hospital stay was 2 days (IQR, 1-3 days). No 30-day readmissions or complications occurred. Eight patients (36%) underwent gastrectomy (CRS ± HIPEC). After an average follow-up period of 11 months, 7 (32%) of the 22 patients were alive. The median overall survival was 11 months (IQR, 195-739 days) from the initial procedure and 19.3 months (IQR, 431-1204 days) from the diagnosis. CONCLUSIONS: Laparoscopic HIPEC appears to be safe with minimal perioperative complications. Approximately one third of the patients undergoing initial laparoscopic HIPEC ultimately proceeded to cytoreduction and gastrectomy. Preliminary survival data from this highly selected cohort suggest that the addition of laparoscopic HIPEC to systemic chemotherapy does not compromise other treatment options. These initial results suggest that laparoscopic HIPEC may offer benefit to patients with GC and PM and aid in the selection of patients who may benefit from curative-intent resection.

[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.

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.

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.