Overview
To determine if the detection of ctDNA after surgical resection of CLM can stratify patients into high and low-risk cohorts for early disease recurrence in order to inform post-operative adjuvant therapy.
Description
Primary Objective:
• To assess 1-year recurrence-free survival rate following liver resection of CLM with curative intent among ctDNA-negative patients who receive risk-stratified postoperative chemotherapy
Secondary Objectives:
- To assess recurrence-free survival following liver resection of CLM with curative intent among ctDNA-positive patients
- To assess overall survival following liver resection among ctDNA-negative and ctDNA-positive patients
- To evaluate the proportion of ctDNA-negative at 1-year post-resection
- To compare survival of ctDNA-negative patients undergoing ctDNA-guided postoperative chemotherapy to historical controls
- To evaluate proportion of patients in each arm who change chemotherapy in response to ctDNA measurement
- To delineate the pattern of disease recurrence
- To assess ctDNA sensitivity and specificity for predicting disease recurrence
- To evaluate MDASI-GI during the course of postoperative therapy
- To evaluate and correlate patient molecular subtypes and characterization of tumor biologic factors that are associated with ctDNA detection
- To evaluate surgery-related adverse events occurring up to 90 days after surgery, and chemo-related adverse events occurring up to 30 days after the last dose of chemotherapy
Outcome Measures:
- Primary
• Recurrence-free survival at 1-year post-hepatectomy among ctDNA-negative patients
- Secondary
-
- Recurrence-free survival at 1-year post-hepatectomy among ctDNA-positive patients
- Overall survival (OS) among ctDNA-negative and ctDNA-positive patients
- ctDNA-negativity at 1-year post-resection
- Proportion of patients in each group with chemotherapy regimen change in response to ctDNA dynamics
- Pattern of disease recurrence (i.e., liver, systemic, salvageable vs. unsalvageable)
- ctDNA sensitivity/specificity for recurrent disease overall by timepoint
- MDASI-GI at clinic visits during course of postoperative therapy
- Tumor radiologic, histologic, and molecular profiling and correlative characterization based upon ctDNA detection
- Adverse events
Eligibility
Inclusion Criteria:
- Patients ≥18 years of age with CLM undergoing elective hepatectomy with curative intent (primary colorectal primary cancer previously removed OR being removed at time of hepatectomy) after preoperative chemotherapy (i.e., FOLFOX/FOLFIRI +/- bevacizumab or panitumumab/cetuximab) from 07/01/2021 - 12/31/2023
- Must receive ≥ 4 cycles of preoperative chemotherapy
Exclusion Criteria:
- Patients with primary colorectal tumor that will remain in situ
- Inability to undergo postoperative chemotherapy, or postoperative chemotherapy not planned a priori
- Unwilling/unable to undergo blood draws for ctDNA, patient or provider-determined
- Other active malignancies requiring treatment
- Women who are pregnant