Discussion
ovarian cancer, nephrotoxicity, B-cell, toxicity, toxicities, nephrotoxicities, uterine cancer, renal toxicity, renal toxicities, acute renal failure, AKI, HIPEC-induced renal toxicities
OVARIAN CANCER, ACUTE INFLAMMATORY RESPONSE, UTERINE CANCER, RENAL FAILURE, RECRUITMENT, RECURRENT CANCER, ACUTE RENAL FAILURE, ONCOLOGY, DISEASE CHARACTERISTIC, COMPLICATIONS
Despite enthusiasm for HIPEC in EOC, routine use of HIPEC is marred by its toxicities and skepticism over its true clinical benefit. Despite a well-established incidence of nephrotoxicity from HIPEC with cisplatin, management and prevention of this toxicity vary widely. The Peritoneal Surface Oncology Group International (PSOGI) recently performed a consensus among international HIPEC experts to derive recommendations regarding the indications and delivery of HIPEC regimens.Despite preferred expert opinions, there have been limited studies investigating HIPEC-specific nephrotoxicities. To date, retrospective studies have compared the nephroprotective effects of ST versus no ST when given in conjunction with HIPEC with cisplatin.A major strength of our study is the evaluation of ST use versus no ST use on renal function as a primary outcome. Although some trials have shown the nephroprotective effect of ST, they have been largely retrospective or observational in design.While the median days to initiation of adjuvant chemotherapy was not statistically significant in our study, a trend favored the ST group in initiating adjuvant chemotherapy sooner than the nST group. There also was a trend toward improved median PFS amongst the ovarian cancer patients analyzed in the ST group compared with the nST group, although this may be due to imbalance of primary EOC predominance in the ST group compared with recurrent EOC predominance in the nST group. In the subcohorts of primary EOC and recurrent EOC, there was no difference in PFS between the nST and ST groups. We sought homogeneity for survival analysis and thus excluded patients with uterine cancer. The uterine cancer cohort was small (We performed transcriptomic analyses in normal peritoneal samples to identify molecular signatures that correlate with HIPEC-induced renal toxicities. These novel analyses investigate what is occurring at a transcriptional level in patients who experience renal toxicity from HIPEC with cisplatin. Gene pathways related to immune modulation were significantly upregulated in patients who experienced renal failure, many of which are related to neutrophil, T-cell, and B-cell activation.The upregulation of inflammatory cells, such as neutrophils and T cells, suggests an acute inflammatory response resulting in AKI. Indeed, immune and inflammatory mechanisms have been recognized as important mediators of cisplatin nephrotoxicity.Our study is limited by the lack of randomization, which led to the nST group preceding the ST group with resultant median follow up differences. ST administration was initiated after interim analysis revealing significant renal toxicities. This limited our ability to exclude possible confounders in our subject selection. This chronological recruitment for both groups accounts for the difference in median follow-up between the nST and ST groups (57.7 vs. 27.7 months), given that nST subjects were recruited first. An additional limitation includes a slight imbalance in disease characteristics between the nST and ST groups. The nST group had more recurrent cancer cases, whereas the ST group had more primary cases. Although it could be assumed that more heavily pretreated, recurrent EOC patients may have worse renal function, baseline Cr between the two groups was similar. Mean operating time and PCI were lower in the nST group. This could be associated with decreased surgical complexity and associated complications in the nST group, thus reducing the likelihood for acute renal failure in this group. BMIs were significantly different between the two groups (ST: 23.4 vs. nST: 28.5, 