Abstract 5604: Circulating tumor DNA for predicting peritoneal only disease recurrence in colon cancer
Authors: Chang Kevin C. , Berg Daniel , Chandrasekharan Chandrika , Steckly Kelsey , Sharif Saima , Chan Carlos H. 
Published: April 2023

Background: Peritoneal Carcinomatosis in Colon Cancer (PCCC) is a major cause of morbidity. Early detection of PCCC is important for early intervention like systemic chemotherapy and cytoreductive surgery (CRS) +/- hyperthermic intraperitoneal chemotherapy (HIPEC). Circulating tumor DNA (ctDNA) testing is a promising method to assess recurrence not detectable yet on imaging, identifying 87.5% of recurrences in Stage I-III CRC with a mean lead-time of 8.7 months. It is unclear if ctDNA testing is sensitive in detection of recurrent PCCC ahead of clinical/radiological presentation.

We report data from 6 CRC patients with PCCC who underwent complete CRS and were followed with serial ctDNA testing.

Methods: In this single institution study, patients with PCCC were included from our prospectively enrolled GI cancer patient cohort (GIMER: IRB #201202743). Peritoneal carcinomatosis at CRS was determined using the Peritoneal Cancer Index. ctDNA concentration in mean tumor molecules/mL of plasma was assessed using a commercially available tumor-informed, personalized ctDNA assay (Signatera™, Natera, Inc.) that uses patient-specific somatic single-nucleotide variants. Plasma samples for ctDNA analysis were collected before surgery, 1, 2, 4, 6 months post-surgery, then every 3 months until a positive ctDNA test triggered CT imaging. Patients also had routine CT imaging every 6 months after surgery.

Results: 5 of 6 patients met endpoint with median time of 35 days from positive ctDNA to recurrence on imaging. In 4 patients, positive ctDNA prompted CT imaging which was negative, but follow-up PET scan was positive. Patient 6 was ctDNA negative and recurrence-free at last follow-up.

Conclusions: This analysis demonstrated the potential of longitudinal ctDNA monitoring for early detection of PCCC recurrence by prompting early imaging. PET was more sensitive in detecting recurrence than CT, and should be considered when determining PCCC recurrence. Enrollment and further analysis of ctDNA continues.

Table 1. Patient Pre-op Chemo Post-chemo, pre-op ctDNA Peritoneal Cancer Index Post-op (1m) ctDNA 2m ctDNA 4m ctDNA 6m ctDNA 9m ctDNA 12m ctDNA 15m ctDNA Recurrence Days between ctDNA positivity and positive imaging Imaging Findings 1 Yes 0 5 0 0 0 0 0.48 - - Yes 6 CT CAP Positive 2 Yes 0 4 0 0 0 0.04 - - - Yes 54 CT CAP Negative; PET Positive 3 Yes 0.28 18 0 0 0 0 0.09 - - Yes 25 CT CAP Negative; PET Positive 4 Yes 0 0 0 0 0 0 0 0 0.18 Yes 35 CT CAP Negative; PET Positive 5 Yes 0.61 5 0 0 0.17 0 0.32 0.12 - Yes 274 CT CAP Negative; PET Positive 6 Yes 0 5 0 - 0 0 - - - No NA CT CAP Negative to date

Citation Format: Kevin C. Chang, Daniel Berg, Chandrika Chandrasekharan, Kelsey Steckly, Saima Sharif, Carlos H. Chan. Circulating tumor DNA for predicting peritoneal only disease recurrence in colon cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5604.