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.

Validation of the AJCC 8th Edition Staging System for Disseminated Appendiceal Cancer Patients Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: A Multi-institutional Analysis.

BACKGROUND: The AJCC 8th edition stratifies stage IV disseminated appendiceal cancer (dAC) patients based on grade and pathology. This study was designed to externally validate the staging system and to identify predictors of long-term survival. METHODS: A 12-institution cohort of dAC patients treated with CRS ± HIPEC was retrospectively analyzed. Overall survival (OS) and recurrence-free survival (RFS) were analyzed by using Kaplan-Meier and log-rank tests. Univariate and multivariate cox-regression was performed to assess factors associated with OS and RFS. RESULTS: Among 1009 patients, 708 had stage IVA and 301 had stage IVB disease. Median OS (120.4 mo vs. 47.2 mo) and RFS (79.3 mo vs. 19.8 mo) was significantly higher in stage IVA compared with IVB patients (p < 0.0001). RFS was greater among IVA-M1a (acellular mucin only) than IV M1b/G1 (well-differentiated cellular dissemination) patients (NR vs. 64 mo, p = 0.0004). Survival significantly differed between mucinous and nonmucinous tumors (OS 106.1 mo vs. 41.0 mo; RFS 46.7 mo vs. 21.2 mo, p < 0.05), and OS differed between well, moderate, and poorly differentiated (120.4 mo vs. 56.3 mo vs. 32.9 mo, p < 0.05). Both stage and grade were independent predictors of OS and RFS on multivariate analysis. Acellular mucin and mucinous histology were associated with better OS and RFS on univariate analysis only. CONCLUSIONS: AJCC 8th edition performed well in predicting outcomes in this large cohort of dAC patients treated with CRS ± HIPEC. Separation of stage IVA patients based on the presence of acellular mucin improved prognostication, which may inform treatment and long-term, follow-up strategies.

Safe performance of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with HIV infection.

BACKGROUND: Patients with HIV (PHIV) are living longer with the adoption of anti-retroviral therapy. As such, more patients are presenting with advanced cancer diagnoses, including peritoneal surface malignancies. The objective of this study was to assess the safety of CRS/HIPEC in this cohort of patients. CASE: Five PHIV were identified, four of whom underwent CRS/HIPEC. Primary sites of disease were low-grade appendiceal mucinous tumors in three patients and peritoneal mesothelioma in the other. Operative time ranged from 7 to 14 h. One patient developed a Clavien grade II complication postoperatively. There was no instance of neutropenia identified. One patient died of disease 19 months after surgery; the remaining three patients are alive 11, 21, and 33 months postoperatively. CONCLUSION: This study demonstrates that CRS/HIPEC can be performed in PHIV without prohibitive complications and operative recovery approximates that of non-HIV patients. Though more study is needed, HIV should not preclude a patient from being offered CRS/HIPEC.

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.

Preoperative Radiographic Assessment Predicts Incomplete Cytoreduction in Patients with Low Grade Mucinous Adenocarcinoma of the Appendix.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for patients with low-grade mucinous adenocarcinoma (LGMA) is most effective when complete cytoreduction is achieved. We externally validated two radiographic scoring systems to predict resectability and assessed radiographic response to systemic chemotherapy (SCT). METHODS: Patients with LGMA who received preoperative SCT followed by CRS/HIPEC from 2013 to 2016 were identified. CT scans were graded by six physicians using the simplified radiologic score (SRS) and simplified preoperative assessment of appendiceal tumor (SPAAT) systems. Positive and negative predictive values (PPV, NPV) were calculated by comparing to completeness of cytoreduction. Inter-rater agreement was assessed using the intraclass correlation coefficient (ICC). RESULTS: Twenty-four patients had preoperative SCT followed by CRS/HIPEC. Thirteen patients underwent incomplete CRS and 11 patients complete CRS. Scoring of the preoperative CT had a PPV of complete cytoreduction of 75% and 66.7% for SRS and SPAAT, respectively. NPV was 83.4% and 88.9% for SRS and SPAAT, respectively. ICC for the preoperative SRS and SPAAT score was 0.826 (95% confidence interval [CI]: 0.720-0.910] and 0.788 [0.667-0.888). Comparison of CT scans before and after SCT recorded an increase in calculated scores in 45.8% (SRS) and 50% (SPAAT) of patients. CONCLUSIONS: External validation of two radiographic scoring systems to predict complete cytoreduction showed that inter-rater agreement for both systems was good. Both scoring systems predicted incomplete cytoreduction. Applying a systematic approach to preoperative imaging review is recommended to improve treatment selection by minimizing morbidity associated with incomplete CRS and help to set patient expectations.

Optimal Surveillance Frequency After CRS/HIPEC for Appendiceal and Colorectal Neoplasms: A Multi-institutional Analysis of the US HIPEC Collaborative.

BACKGROUND: No guidelines exist for surveillance following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for appendiceal and colorectal cancer. The primary objective was to define the optimal surveillance frequency after CRS/HIPEC. METHODS: The U.S. HIPEC Collaborative database (2000-2017) was reviewed for patients who underwent a CCR0/1 CRS/HIPEC for appendiceal or colorectal cancer. Radiologic surveillance frequency was divided into two categories: low-frequency surveillance (LFS) at q6-12mos or high-frequency surveillance (HFS) at q2-4mos. Primary outcome was overall survival (OS). RESULTS: Among 975 patients, the median age was 55 year, 41% were male: 31% had non-invasive appendiceal (n = 301), 45% invasive appendiceal (n = 435), and 24% colorectal cancer (CRC; n = 239). With a median follow-up time of 25 mos, the median time to recurrence was 12 mos. Despite less surveillance, LFS patients had no decrease in median OS (non-invasive appendiceal: 106 vs. 65 mos, p < 0.01; invasive appendiceal: 120 vs. 73 mos, p = 0.02; colorectal cancer [CRC]: 35 vs. 30 mos, p = 0.8). LFS patients had lower median PCI scores compared with HFS (non-invasive appendiceal: 10 vs. 19; invasive appendiceal: 10 vs. 14; CRC: 8 vs. 11; all p < 0.01). However, on multivariable analysis, accounting for PCI score, LFS was still not associated with decreased OS for any histologic type (non-invasive appendiceal: hazard ratio [HR]: 0.28, p = 0.1; invasive appendiceal: HR: 0.73, p = 0.42; CRC: HR: 1.14, p = 0.59). When estimating annual incident cases of CRS/HIPEC at 375 for non-invasive appendiceal, 375 invasive appendiceal and 4410 colorectal, LFS compared with HFS for the initial two post-operative years would potentially save $13-19 M/year to the U.S. healthcare system. CONCLUSIONS: Low-frequency surveillance after CRS/HIPEC for appendiceal or colorectal cancer is not associated with decreased survival, and when considering decreased costs, may optimize resource utilization.