Association of circulating DNA with recurrence in CRS-HIPEC patients with colorectal and appendiceal peritoneal carcinomatosis: Insights from a phase II randomized trial.

person Anup Kasi University of Kansas Cancer Center, Westwood, KS info_outline Anup Kasi, Raed Moh'd Taiseer Al-Rajabi, Anwaar Saeed, Weijing Sun, Joaquina Celebre Baranda, Haoran Li, Jo Wick, Sanjana Mullangi, Kenda Eberhardt, Shannon Bradbury, Rebecca Romero, Erin Carroll, Lori Barbosa, Mazin Francis Al-Kasspooles

Authors person Anup Kasi University of Kansas Cancer Center, Westwood, KS info_outline Anup Kasi, Raed Moh'd Taiseer Al-Rajabi, Anwaar Saeed, Weijing Sun, Joaquina Celebre Baranda, Haoran Li, Jo Wick, Sanjana Mullangi, Kenda Eberhardt, Shannon Bradbury, Rebecca Romero, Erin Carroll, Lori Barbosa, Mazin Francis Al-Kasspooles Organizations University of Kansas Cancer Center, Westwood, KS, Division of Medical Oncology, University of Kansas Medical Center, Kansas City, KS, Department of Medical Oncology, University of Pittsburgh, Pittsburgh, PA, University of Kansas Medical Center, Kansas City, KS, University of Kansas Cancer Center, Fairway, KS, University of Kansas Medical Center, Department of Biostatistics & Data Science, Kansas City, KS, University of Kansas Medical Center, Westwood, KS, Kansas University Cancer Center, Westwood, KS, Kansas University Cancer Center, Kansas City, KS Abstract Disclosures Research Funding KUCC Background: There is a need for biomarkers to guide patient selection for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) in cases of peritoneal carcinomatosis from colorectal and appendiceal cancer. SigNatera is a blood-based quantitative test to detect colorectal cancer recurrence by indicating the presence of at least two altered colorectal cancer-associated genes in Circulating tumor DNA (ctDNA). We performed a correlative study to help determine if using SigNatera ctDNA would be a predictive and prognostic biomarker of recurrent cancer in patients who underwent CRS-HIPEC on a Phase II Randomized Trial Comparing Morbidity and Mortality of CRS-HIPEC using Mitomycin-C versus Melphalan for Colorectal and Appendiceal Peritoneal Carcinomatosis. Methods: 30 patients on the phase II trial had the option for consenting for the ctDNA correlative study utilizing SigNatera sponsored by Natera. Pre-op samples were collected prior to CRS-HIPEC on Day 0 and post-op samples ~2 weeks post-hospital discharge, followed by every 3 months x 2 years. The exploratory objective of the prognostic impact of ctDNA is evaluated by correlating pre-op ctDNA status and Disease-Free Survival (DFS) Results: All 30 pts that underwent ctDNA testing were treated with neoadjuvant chemotherapy prior to CRS-HIPEC. Pre-op ctDNA was negative in 20 pts (8 recurrences, median DFS = 15.9 months) and positive in 10 pts (7 recurrences, median DFS = 39.9 months), p =0.19. Of the 20 pre-op ctDNA(-) pts, 18 remained ctDNA(-) in post-op (12 recurrences, median DFS = 15.6 months) and 2 turned ctDNA(+) (0 recurrences). Of the 10 pre-op ctDNA(+) pts, 2 remained ctDNA(+) post-op (1 recurrence, median DFS = 9.5 months) and 8 turned ctDNA(-) (2 recurrences, median DFS = 39.9 months), p=0.1. Conclusions: The unexpected numerically favorable DFS in the pre-op ctDNA(+) group, in comparison to the pre-op ctDNA(-) group, challenges the utility of preop ctDNA status in guiding CRS + HIPEC decision-making. Though limited by small sample size, this finding may be likely due to the impact of post-op therapy which notably converted 10 preop ctDNA(+) pts to post-op ctDNA(-) status. Our findings warrant validation in a larger study to unravel the multifaceted factors influencing ctDNA’s prognostic value. Clinical trial information: NCT03073694. # - FOLFOX, FOLFIRI with or without antibody $ - FOLFOXIRI, FOLFIRINOX with or without antibody. ctDNA Positive (10 pts) ctDNA Negative (20 pts) Median Age 61 57 Sex, No (%) M/F 2(20%)/8(80%) 11(55%)/9(45%) Race, No (%) W/AA 10(100%)/0(0%) 19(95%)/1(5%) Ethnicity, No(%) Non Hispanic 10(100%) 20(100%) Colon/Appendix 9(90%)/1(10%) 13(65%)/7(35%) Doublet # /Triplet Chemo $ 7(70%)/3(30%) 10(50%)/10(50%) HIPEC Mitomycin-C/Melphalan 5(50%)/5(50%) 9(45%)/11(55%) Recurrence: No/Yes 3(30%)/7(70%) 12(60%)/8(40%)

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