Development of a predictive model for risk stratification of acute kidney injury in patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

Acute kidney injury (AKI) following hyperthermic intraperitoneal chemotherapy (HIPEC) is common. Identifying patients at risk could have implications for surgical and anesthetic management. We aimed to develop a predictive model that could predict AKI based on patients' preoperative characteristics and intraperitoneal chemotherapy regimen. We retrospectively gathered data of adult patients undergoing HIPEC at our health system between November 2013 and April 2022. Next, we developed a model predicting postoperative AKI using multivariable logistic regression and calculated the performance of the model (area under the receiver operating characteristics curve [AUC]) via tenfold cross-validation. A total of 412 patients were included, of which 36 (8.7%) developed postoperative AKI. Based on our multivariable logistic regression model, multiple preoperative and intraoperative characteristics were associated with AKI. We included the total intraoperative cisplatin dose, body mass index, male sex, and preoperative hemoglobin level in the final model. The mean area under the receiver operating characteristics curve value was 0.82 (95% confidence interval 0.71-0.93). Our risk model predicted AKI with high accuracy in patients undergoing HIPEC in our institution. The external validity of our model should now be tested in independent and prospective patient cohorts.

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.

Neighborhood-Level Socioeconomic Disadvantage Predicts Outcomes in Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Malignancy.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) improves survival in select patients with peritoneal metastases (PM), but the impact of social determinants of health on CRS/HIPEC outcomes remains unclear. PATIENTS AND METHODS: A retrospective review was conducted of a multi-institutional database of patients with PM who underwent CRS/HIPEC in the USA between 2000 and 2017. The area deprivation index (ADI) was linked to the patient's residential address. Patients were categorized as living in low (1-49) or high (50-100) ADI residences, with increasing scores indicating higher socioeconomic disadvantage. The primary outcome was overall survival (OS). Secondary outcomes included perioperative complications, hospital/intensive care unit (ICU) length of stay (LOS), and disease-free survival (DFS). RESULTS: Among 1675 patients 1061 (63.3%) resided in low ADI areas and 614 (36.7%) high ADI areas. Appendiceal tumors (n = 1102, 65.8%) and colon cancer (n = 322, 19.2%) were the most common histologies. On multivariate analysis, high ADI was not associated with increased perioperative complications, hospital/ICU LOS, or DFS. High ADI was associated with worse OS (median not reached versus 49 months; 5 year OS 61.0% versus 28.2%, P < 0.0001). On multivariate Cox-regression analysis, high ADI (HR, 2.26; 95% CI 1.13-4.50; P < 0.001), cancer recurrence (HR, 2.26; 95% CI 1.61-3.20; P < 0.0001), increases in peritoneal carcinomatosis index (HR, 1.03; 95% CI 1.01-1.05; P < 0.001), and incomplete cytoreduction (HR, 4.48; 95% CI 3.01-6.53; P < 0.0001) were associated with worse OS. CONCLUSIONS: Even after controlling for cancer-specific variables, adverse outcomes persisted in association with neighborhood-level socioeconomic disadvantage. The individual and structural-level factors leading to these cancer disparities warrant further investigation to improve outcomes for all patients with peritoneal malignancies.

Role of Circulating Tumor DNA Among Patients with Colorectal Peritoneal Metastases.

PURPOSE: This was a review of circulating tumor DNA (ctDNA) in patients with peritoneal metastases from colorectal cancer. METHODS: We searched the PubMed database for studies reporting detection of ctDNA in patients with colorectal cancer (CRC) and with peritoneal metastases (PM) from colorectal cancer (CRPM). We extracted data on the population included, number of subjects, study design, type of ctDNA assay used and schedule, and the major findings from these publications. RESULTS: We identified 13 studies for review investigating ctDNA, using a variety of ctDNA assays, among 1787 patients with CRC without PM, as well as four eligible published and one unpublished (in press) studies, which included 255 patients with PM from any primary site and 61 patients with CRPM. Among the 13 studies investigating ctDNA among CRC without PM, posttreatment surveillance ctDNA was associated with recurrence and was generally more sensitive than imaging or tumor markers. Among the five studies including patients with PM, ctDNA was not universally able to detect the presence of PM, but when present, ctDNA predicted worse outcomes. CONCLUSION: Circulating-tumor DNA is a potentially useful surveillance tool for patients with CRC. However, the sensitivity of ctDNA to detect CRPM is variable and warrants further inquiry.

Influence of insurance status on the postoperative outcomes of cytoreductive surgery and HIPEC.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is increasingly performed for peritoneal surface malignancies but remains associated with significant morbidity. Scant research is available regarding the impact of insurance status on postoperative outcomes. METHODS: Patients undergoing CRS/HIPEC between 2000 and 2017 at 12 participating sites in the US HIPEC Collaborative were identified. Univariate and multivariate analyses were used to compare the baseline characteristics, operative variables, and postoperative outcomes of patients with government, private, or no insurance. RESULTS: Among 2268 patients, 699 (30.8%) had government insurance, 1453 (64.0%) had private, and 116 (5.1%) were uninsured. Patients with government insurance were older, more likely to be non-white, and comorbid (p < 0.05). Patients with government (OR: 2.25, CI: 1.50-3.36, p < 0.001) and private (OR: 1.69, CI: 1.15-2.49, p = 0.008) insurance had an increased risk of complications on univariate analysis. There was no independent relationship on multivariate analysis. An American Society of Anesthesiologists score of 3 or 4, peritoneal carcinomatosis index score >15, completeness of cytoreduction score >1, and nonhome discharge were factors independently associated with a postoperative complication. CONCLUSION: While there were differences in postoperative outcomes between the three insurance groups on univariate analysis, there was no independent association between insurance status and postoperative complications after CRS/HIPEC.

Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: a prospective clinical trial and comparative analysis.

BACKGROUND: Open cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with high morbidity, which limits the degree to which patients may benefit from this therapy. This study aimed to determine the feasibility of laparoscopic CRS/HIPEC. METHODS: This was a single institution prospective clinical trial and comparative study using historical controls. Patients with histologically confirmed peritoneal surface malignancy (PSM) of appendiceal, colorectal, ovarian, or primary peritoneal origin, peritoneal carcinomatosis index (PCI) [Formula: see text] 10 were eligible. RESULTS: Clinical trial: 18 patients (median age 57 years, 39% female) with appendiceal (15) or colorectal (3) primary PSM underwent laparoscopic CRS/HIPEC. Median and range outcomes were: operative time 219 min (134-378), EBL 10 mL (0-100), time to return to bowel function 3 days (1-7), duration IV narcotic use 3 days (1-8), length of stay 6 days (3-11). All patients had a complete cytoreduction (CC-score 0). Three (17%) experienced minor morbidity, with no major morbidity or mortality. Median DFS and OS were not reached with median follow-up of 48 months. Comparative analysis: Laparoscopic approach associated with reduced time to return of bowel function (3 versus 4 days, p = 0.001), length of stay (8 versus 5 days, p < 0.001), and morbidity (16% versus 42%, p = 0.008). Independent predictors of DFS included prior chemotherapy (HR 5.07, 95% CI 1.85, 13.89; p = 0.002), and CC-score > 0 (HR 3.31, 95% CI 1.19, 9.41; p = 0.025), but not surgical approach. CC-score > 0 was the only independent predictor of OS (HR 10.12, 95% CI 2.16, 47.30, p = 0.003). CONCLUSIONS AND RELEVANCE: Laparoscopic CRS/HIPEC should be considered for patients with PSM with low-volume disease, including those with adenocarcinoma histology. TRIAL REGISTRATION: Clinicaltrials.gov; NCT02463877.

Alvimopan for Enhanced Gastrointestinal Recovery after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: A Randomized Controlled Trial.

BACKGROUND: Surgical management of peritoneal metastases with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is associated with prolonged length of stay and time to return of bowel function. Alvimopan is a peripherally acting opioid antagonist that reduces postoperative ileus. We sought to determine the efficacy of alvimopan on return of bowel function in patients undergoing CRS-HIPEC. METHODS: A double-blind, randomized, placebo-controlled, single-institution, IRB-approved trial was conducted in patients undergoing CRS-HIPEC from March 2018 to April 2020. Patients received alvimopan or placebo preoperatively and twice daily postoperatively for 7 days. The primary endpoint (GI-2) was the time of tolerance of solid food and first bowel movement (BM). Secondary endpoints were the proportion of patients with prolonged ileus, time to first flatus, first BM, tolerance of solid food, discharge, and adverse events (AEs). RESULTS: Sixty-two patients met eligibility criteria and received placebo (n = 32) or alvimopan (n = 30), and were included in the analysis. The median time to GI-2 was 152 hours (95% CI 134, 204) in the placebo arm versus 117 hours (95% CI 102, 158) in the alvimopan arm (p = 0.04). The time to BM was 89 hours (95% CI 71, 114) in the placebo arm vs 67 hours (95% CI 62, 89) in the alvimopan arm (p = 0.02). There were no significant differences in AE rates, proportion of patients with prolonged ileus, or other secondary endpoints. CONCLUSION: Perioperative alvimopan was well tolerated and accelerated bowel function recovery in patients undergoing CRS-HIPEC.

Co-Localization of Gastrointestinal Stromal Tumors (GIST) and Peritoneal Mesothelioma: A Case Series.

PURPOSE: Gastrointestinal stromal tumor (GIST) is associated with increased risk of additional cancers. In this study, synchronous GIST, and peritoneal mesothelioma (PM) were characterized to evaluate the relationship between these two cancers. METHODS: A retrospective chart review was conducted for patients diagnosed with both GIST and PM between July 2010 and June 2021. Patient demographics, past tumor history, intraoperative reports, cross-sectional imaging, peritoneal cancer index (PCI) scoring, somatic next-generation sequencing (NGS) analysis, and histology were reviewed. RESULTS: Of 137 patients who underwent primary GIST resection from July 2010 to June 2021, 8 (5.8%) were found to have synchronous PM, and 4 patients (50%) had additional cancers and/or benign tumors. Five (62.5%) were male, and the median age at GIST diagnosis was 57 years (range: 45-76). Seventy-five percent of GISTs originated from the stomach. Of the eight patients, one patient had synchronous malignant mesothelioma (MM), and the remaining had well-differentiated papillary mesothelioma (WDPM), which were primarily located in the region of the primary GIST (89%). The median PCI score was 2 in the WDPM patients. NGS of GIST revealed oncogenic KIT exon 11 (62.5%), PDGFRA D842V (25%), or SDH (12.5%) mutations, while NGS of the MM revealed BAP1 and PBRM1 alterations. CONCLUSIONS: One in 17 GIST patients undergoing resection in this series have PM, which is significantly higher than expected if these two diseases were considered as independent events. Our results indicate that synchronous co-occurrence of GIST and PM is an underrecognized finding, suggesting a possible relationship that deserves further investigation.

Prognostic Significance of Preoperative Tumor Markers in Pseudomyxoma Peritonei from Low-Grade Appendiceal Mucinous Neoplasm: a Study from the US HIPEC Collaborative.

BACKGROUND: Tumor markers are commonly utilized in the diagnostic evaluation, treatment decision making, and surveillance of appendiceal tumors. In this study, we aimed to determine the prognostic significance of elevated preoperative tumor markers in patients with pseudomyxoma peritonei secondary to low-grade appendiceal mucinous neoplasm who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. METHODS: Using a multi-institutional database, eligible patients with measured preoperative tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), or cancer antigen 125 (CA-125)] were identified. Univariate and multivariate Cox-proportional hazards regression analysis assessed relationships between normal and elevated serum tumor markers with progression-free and overall survival in the context of multiple clinicopathologic variables. RESULTS: zTwo hundred and sixty-four patients met criteria. CEA was the most commonly measured tumor marker (97%). Patients who had any elevated tumor marker had a higher peritoneal carcinomatosis index (PCI) as compared to those with normal range markers. Elevated CEA and CA 19-9 levels were individually associated with longer inpatient length of stay, requirement for intraoperative transfusion, and incomplete cytoreduction. Utilization of neoadjuvant chemotherapy, increased PCI score, elevated CA 19-9 (p = 0.007), and CA-125 levels (p = 0.01) were predictive of decreased progression-free survival on univariate analysis. However, in a multivariate model, only elevated PCI was a statistically significant predictor of progression-free survival. CONCLUSION: Elevated preoperative tumor markers indicate a higher burden of disease but are not independently associated with survival in this retrospective multi-institutional cohort. Further prospective studies are needed to clarify the utility of these markers in this patient population.

The Utility of Preoperative Tumor Markers in Peritoneal Carcinomatosis from Primary Appendiceal Adenocarcinoma: an Analysis from the US HIPEC Collaborative.

BACKGROUND: Prognostication based on preoperative clinical factors is lacking in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). This study aims to determine the value of preoperative tumor markers as predictors of progression-free survival (PFS) and overall survival (OS) for patients with peritoneal carcinomatosis from a primary mucinous adenocarcinoma of the appendix (MACA). METHODS: We queried the United States HIPEC Collaborative, a database of patients with peritoneal carcinomatosis treated with CRS/HIPEC at twelve institutions between 2000 and 2017, identifying 409 patients with MACA. Multivariate analysis was used to identify independent predictors of disease progression. Subgroup analysis was conducted to evaluate the impact of tumor grade on the predictive value of tumor markers. RESULTS: CA19-9 [HR 2.44, CI 1.2-3.4] emerged as an independent predictor of PFS while CEA [HR 4.98, CI 1.06-23.46] was independently predictive of OS (p <0.01). Tumor differentiation was the most potent predictor of both PFS (poorly differentiated vs well, [HR 4.5 CI 2.01-9.94]) and OS ([poorly differentiated vs well-differentiated: [HR 13.5, CI 3.16-57.78]), p <0.05. Among patients with combined CA19-9 elevation and poorly differentiated histology, 86% recurred within a year of CRS/HIPEC (p < 0.01). Similarly, the coexistence of CEA elevation and unfavorable histology led to the lowest survival rate at two years [36%, p < 0.01]. CA-125 was not predictive of PFS or OS. CONCLUSION: Elevated preoperative CA19-9 portends worse PFS, while elevated CEA predicts worse OS after CRS/HIPEC in patients with MACA. This study provides additional evidence that CA19-9 and CEA levels should be collected during standard preoperative bloodwork, while CA-125 can likely be omitted. Tumor differentiation, when added to preoperative tumor marker levels, provides powerful prognostic information. Prospective studies are required to confirm this association.

Impact of Perioperative Blood Transfusions on Outcomes After Hyperthermic Intraperitoneal Chemotherapy: A Propensity-Matched Analysis.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a major operation frequently necessitating red blood cell transfusion. Using multi-institutional data from the U.S. HIPEC Collaborative, this study sought to determine the association of perioperative allogenic blood transfusion (PABT) with perioperative outcomes after CRS/HIPEC. METHODS: This retrospective cohort study analyzed patients who underwent CRS/HIPEC for peritoneal surface malignancy between 2000 and 2017. Propensity score-matching was performed to mitigate bias. Univariate analysis was used to compare demographic, preoperative, intraoperative, and postoperative variables. Factors independently associated with PABT were identified using multivariate analysis. RESULTS: The inclusion criteria were met by 1717 patients, 510 (29.7%) of whom required PABT. The mean Peritoneal Cancer Index (PCI) of our cohort was 14.8 ± 9.3. Propensity score-matching showed an independent association between PABT and postoperative risk of pleural effusion, hemorrhage, pulmonary embolism, enteric fistula formation, Clavien-Dindo grades 3 and 4 morbidity, longer hospital stay, and reoperation (all P < 0.05 in the multivariate analysis). Compared with the patients who received 1 to 5 red blood cell (RBC) units, the patients who received more than 5 units had a greater risk of renal impairment, a longer intensive care unit (ICU) stay, and more postoperative infections. Finally, PABT was an independent predictor of worse survival for patients with appendiceal and colorectal primaries. CONCLUSION: Even low levels of PABT for patients undergoing CRS/HIPEC are independently associated with a greater risk of infectious and non-infectious postoperative complications, and this risk is increased for patients receiving more than 5 RBC units. Worse survival was independently predicted by PABT for patients with peritoneal carcinomatosis of an appendiceal or colorectal origin.

A multi-institutional analysis of Textbook Outcomes among patients undergoing cytoreductive surgery for peritoneal surface malignancies.

BACKGROUND: While recent studies have introduced the composite measure of a textbook outcome (TO) for measuring postoperative outcomes, the incidence of a TO has not been characterized among patients undergoing cytoreductive surgery (CRS) for peritoneal surface malignancies (PSM). STUDY DESIGN: All patients who underwent CRS ± hyperthermic intraperitoneal chemotherapy (HIPEC) between 1999 and 2017 from 12 institutions were included. A TO was defined as the absence of any of the following criteria: completeness of cytoreduction >1, reoperation within 90-days, readmission within 90-days, mortality within 90-days, any grade ≥2 complication, hospital stay >75th percentile, and non-home discharge. RESULTS: Among 1904 patients who underwent CRS, only 30.9% achieved a TO while 69.1% failed to achieve a TO most commonly because of postoperative complications. On multivariable analysis, factors associated with achieving a TO were age <65 years (OR: 1.5), albumin ≥3.5 g/dl (OR: 5.7), receipt of HIPEC (OR: 4.5), PCI ≤14 (OR: 2.2), intravenous fluid volume ≤10,000 ml (OR: 2.1), blood loss ≤1000 ml (OR: 4.2) and operative time <7 h (OR: 1.9); while receipt of neoadjuvant therapy (OR: 0.7) and liver resection (OR: 0.4) were associated with not achieving a TO (all p < 0.05). TO was associated with improved overall survival (median 159 months vs 56 months, p < 0.01) even after controlling for confounders on Cox regression (hazard ratio: 2.5, p < 0.01). CONCLUSION: Among patients undergoing CRS ± HIPEC for PSM, failure to achieve a TO is common and independently associated with worse overall survival.

A Multi-institutional Study of Peritoneal Recurrence Following Resection of Low-grade Appendiceal Mucinous Neoplasms.

BACKGROUND: Peritoneal dissemination of low-grade appendiceal mucinous neoplasms (LAMNs), sometimes referred to as pseudomyxoma peritonei, can result in significant morbidity and mortality. Little is known about the natural history of localized (non-disseminated) LAMNs. OBJECTIVE: The goal of this study was to evaluate the risk of peritoneal recurrence in patients with localized LAMNs. METHODS: We performed a multi-institutional retrospective review of patients with pathologically confirmed localized LAMNs. Baseline characteristics, pathology, and follow-up data were collected. The primary endpoint was the rate of peritoneal recurrence. RESULTS: We identified 217 patients with localized LAMNs. Median age was 59 years (11-95) and 131 (60%) patients were female. Surgical management included appendectomy for 124 (57.1%) patients, appendectomy with partial cecectomy for 26 (12.0%) patients, and colectomy for 67 (30.9%) patients. Pathology revealed perforation in 46 patients (37.7% of 122 patients with perforation status mentioned in the report), extra-appendiceal acellular mucin (EAM) in 49 (22.6%) patients, and extra-appendiceal neoplastic cells (EAC) in 13 (6.0%) patients. Median follow-up was 51.1 months (0-271). Seven (3.2%) patients developed a peritoneal recurrence, with a median time to recurrence of 14.4 months (2.5-47.0). Seven (15.2%) patients with histologic evidence of perforation had recurrence, versus no patients (0%) without perforation (p < 0.001); five (10.2%) patients with EAM versus two (1.2%) patients without EAM (p = 0.007), and one (7.7%) patient with EAC versus six (2.9%) patients without EAC (p = 0.355) had recurrence. CONCLUSIONS: This multi-institutional study represents the largest reported series of patients with localized LAMNs. In the absence of perforation or extra-appendiceal mucin or cells, recurrence was extremely rare; however, patients with any of these pathologic findings require careful follow-up.

A novel preoperative risk score to optimize patient selection for performing concomitant liver resection with cytoreductive surgery/HIPEC.

BACKGROUND: While parenchymal hepatic metastases were previously considered a contraindication to cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC), liver resection (LR) is increasingly performed with CRS/HIPEC. METHODS: Patients from the US HIPEC Collaborative (2000-2017) with invasive appendiceal or colorectal adenocarcinoma undergoing primary, curative intent CRS/HIPEC with CC0-1 resection were included. LR was defined as a formal parenchymal resection. Primary endpoints were postoperative complications and overall survival (OS). RESULTS: A total of 658 patients were included. About 83 (15%) underwent LR of colorectal (58%) or invasive appendiceal (42%) metastases. LR patients had more complications (81% vs. 60%; p = .001), greater number of complications (2.3 vs. 1.5; p < .001) per patient and required more reoperations (22% vs. 11%; p = .007) and readmissions (39% vs. 25%; p = .014) than non-LR patients. LR patients had decreased OS (2-year OS 62% vs. 79%, p < .001), even when accounting for peritoneal carcinomatosis index and histology type. Preoperative factors associated with decreased OS on multivariable analysis in LR patients included age < 60 years (HR, 3.61; 95% CI, 1.10-11.81), colorectal histology (HR, 3.84; 95% CI, 1.69-12.65), and multiple liver tumors (HR, 3.45; 95% CI, 1.21-9.85) (all p < .05). When assigning one point for each factor, there was an incremental decrease in 2-year survival as the risk score increased from 0 to 3 (0: 100%; 1: 91%; 2: 58%; 3: 0%). CONCLUSIONS: As CRS/HIPEC + LR has become more common, we created a simple risk score to stratify patients considered for CRS/HIPEC + LR. These data aid in striking the balance between an increased perioperative complication profile with the potential for improvement in OS.

Preoperative bevacizumab does not increase complications following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Preoperative bevacizumab has been reported to increase postoperative complication risk following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). We sought to review our experience with preoperative bevacizumab in patients undergoing CRS/HIPEC for peritoneal surface malignancy. METHODS: This is a retrospective review of patients who received neoadjuvant systemic therapy with or without bevacizumab prior to CRS/HIPEC at a high-volume academic center from 2007-2018. RESULTS: Of 499 patients, a total of 88 patients received neoadjuvant chemotherapy alone (n = 34) or in combination with bevacizumab (n = 54) within 3 months prior to CRS/HIPEC. No differences existed in 60-day major morbidity (17.6 vs. 16.7%, p = 0.81) or 60-day mortality (0 vs. 0%) between the two cohorts, and neoadjuvant bevacizumab was not associated with increased odds of overall complications (OR 0.86, 95% CI 0.35-2.09, p = 0.73) or major morbidity (OR 0.86, 95% CI 0.24-3.00, p = 0.81). Stratifying patients by primary tumor origin and post-operative complications did not reveal any significant differences between the two treatment groups. In addition, progression-free survival (PFS) and overall survival (OS) were similar in both cohorts. CONCLUSIONS: Preoperative bevacizumab is not associated with increased morbidity or mortality following CRS/HIPEC. Neoadjuvant therapy employing this biologic agent is safe and should not be a deterrent for aggressive cytoreduction with curative intent.

CRS/HIPEC with Major Organ Resection in Peritoneal Mesothelioma Does not Impact Major Complications or Overall Survival: A Retrospective Cohort Study of the US HIPEC Collaborative.

INTRODUCTION: CRS/HIPEC is thought to confer a survival advantage for patients with malignant peritoneal mesothelioma (MPM). However, the impact of nonperitoneal organ resection is not clearly defined. We evaluated the impact of major organ resection (MOR) on postoperative outcomes and overall survival (OS). PATIENTS AND METHODS: The US HIPEC collaborative database (2000-2017) was reviewed for MPM patients who underwent CRS/HIPEC. MOR was defined as total or partial resection of diaphragm, stomach, spleen, pancreas, small bowel, colon, rectum, kidney, ureter, bladder, and/or uterus. MOR was categorized as 0, 1, or 2+ organs. RESULTS: A total of 174 patients were identified. Median PCI was 16 (3-39). The distribution of patients with MOR-0, MOR-1, and MOR-2+ was 94, 45, and 35 patients, respectively. MOR-1 and MOR-2+ groups had a higher frequency of any complication compared with MOR-0 (57.8%, 74.3%, and 48.9%, respectively, p = 0.035), but Clavien 3/4 complications were similar. Median length of stay was slightly higher in the MOR-1 and MOR-2+ groups (10 and 11 days) compared with the MOR-0 cohort (9 days, p = 0.005). Incomplete cytoreduction, ASA class 4, and male gender were associated with increased mortality on unadjusted analysis; however, their impact on OS was attenuated on multivariable analysis. MOR was not associated with OS based on these data (MOR-1: HR 1.67, 95% CI 0.59-4.74; MOR-2+ : HR 0.77, 95% CI 0.22-2.69). CONCLUSIONS: MOR was not associated with an increase in major complications or worse OS in patients undergoing CRS/HIPEC for MPM and should be considered, if necessary, to achieve complete cytoreduction for MPM patients.