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Heated Intraperitoneal Chemotherapy After PRODIGE-7: An Institutional Review Of Evolving Practice Patterns
*Fasih Ali Ahmed1, *Malaak Saadah2, *Hanna Kakish1, Jeffrey Hardacre1, Luke Rothermel1, *Richard Hoehn1, *John Ammori1
1University Hospitals Cleveland Medical Center, Cleveland, OH;2Case Western Reserve University School of Medicine, Cleveland, OH

Objective
Cytoreductive surgery (CRS) with Heated Intraperitoneal Chemotherapy (HIPEC) is utilized for well-selected patients with peritoneal surface malignancies. Following the PRODIGE-7 trial in 2018, CRS without HIPEC was proposed having equivalent survival with fewer adverse effects. We examined HIPEC use and post-operative outcomes before and after the PRODIGE-7 results at a single academic center.
Method
We reviewed all patients who underwent CRS with or without HIPEC by our surgical oncology team between 2011 and 2022. Cases were grouped into two time periods (1:2011-2018, 2:2019-2022) before and after the results of PRODIGE-7 trial. Primary outcome of interest was the change in HIPEC use, with secondary outcomes of 90-day post-operative morbidity, readmission, and mortality.
Results
A total of 88 patients were included in this analysis; 47 (55%) and 25 (29%) of whom had a peritoneal metastases of appendiceal and colorectal origin, respectively. The median Peritoneal Carcinomatosis Index (PCI) was 10 (interquartile range (IQR): 4-18.5) and Completeness of Cytoreduction score was 0. A total of 42 (48%) patients experienced a 90-day morbidity, most commonly gastrointestinal complications (18%). Median length of stay was 8 days and there were 16 (18%) 90-day readmissions and 2 (2%) mortalities. 44 (90%) and 23 (61%) patients received HIPEC before and after PRODIGE-7, respectively. Their median PCI in time periods 1 and 2 were 8 (IQR: 3-17) and 11.5 (IQR: 4-19), respectively. There was a reduction in the use of HIPEC among patients requiring major gastrointestinal (GI) visceral resections after 2018; among patients who underwent colectomy, HIPEC was only used in 5 (22%) compared to 23 (52%) before 2018. On multivariable analysis, postoperative adverse events were more likely for patients with PCI of 20+ (OR: 13.62, 95% CI=2.09-88.57) and less likely for patients treated after PROIDGE-7 (OR: 0.28, 95% CI=0.08-0.98) or who underwent HIPEC (OR: 0.17, 95% CI=0.04-0.72).
Conclusion
At our institution, the PRODIGE-7 results impacted practice by reducing the use of HIPEC for higher PCI patients and those requiring major GI visceral resections.

Table 1. Any morbidity/mortality before and after PRODIGE-7
2011-2018 (before PRODIGE-7)2019-2022 (after PRODIGE-7)
CRS aloneCRS+HIPECP-valueCRS aloneCRS+HIPECP-value
Total Number of Patients5 (10%)44 (90%)15 (39%)23 (61%)
Any morbidity/mortality within 90 days5 (100%)21 (48%)0.0269 (60%)6 (26%)0.037
PCI score, median (IQR)10 (6, 10)8 (3, 17)0.5315 (6, 21)11.5 (4, 19)0.31
CC score, median (IQR)0 (0,0)0 (0,0)0.621 (0, 2)1 (0, 1)0.45
Primary Site
Appendiceal4 (80%)23 (52%)0.548 (57%)12 (55%)0.22
Colorectal0 (0%)15 (34%)4 (29%)6 (27%)
Gastric (Antrum)0 (0%)1 (2%)0 (0%)0 (0%)
Mesothelioma1 (20%)4 (9%)0 (0%)4 (18%)
Small Bowel0 (0%)0 (0%)1 (7%)0 (0%)
Unknown0 (0%)1 (2%)1 (7%)0 (0%)
Histology
Adenocarcinoma0 (0%)16 (36%)0.424 (33%)7 (32%)0.29
Mucinous Adenocarcinoma4 (80%)22 (50%)4 (33%)2 (9%)
Mesothelioma1 (20%)3 (7%)0 (0%)4 (18%)
LAMN0 (0%)1 (2%)3 (25%)6 (27%)
Other0 (0%)2 (5%)1 (8%)3 (14%)


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