Objective: To characterize associations between carbohydrate antigen 19–9 (CA19–9) dynamics during neoadjuvant therapy (NT) and survival for patients with pancreatic ductal adenocarcinoma (PDAC). Background: Although normalization of CA19–9 during NT is associated with improved outcomes following PDAC resection, we hypothesize that CA19–9 dynamics during NT can improve prognostication. Methods: Characteristics for patients with PDAC undergoing NT (July 2011–October 2018) with ≥3 CA19–9 results (bilirubin<2mg/dL) were collected and grouped by CA19–9 dynamics. Nonproducers (<1 U/ml) were excluded, and normal was ≤35 U/ml. Postresection survival was compared among groups. Results: Of 431 patients, 166 had eligible CA19–9 values. Median baseline CA19–9 was 98 U/ml. Overall 2-year postresection recurrence-free survival (RFS) and overall survival (OS) were 37% and 63%, respectively. Patients with normalization (53%) had improved 2-year RFS (47% vs. 28%, P = 0.01) and OS (75% vs. 49%, P = 0.01). CA19–9 dynamics during NT were analyzed by shape, direction, and normalization creating response types (“A-B-C-D-E”). Type A was “Always” decreasing to normalization, B “Bidirectional” with eventual normalization, C “Consistently” normal, D any “Decrease” without normalization, and E “Elevating” without normalization. Types A and B responses were associated with the longest postresection 2-year RFS (51% and 56%) and OS (75% and 92%, respectively) whereas Types D and E had the worst outcomes. After adjusting for node-positivity, perineural invasion, and margin-positivity, CA19–9 response types were independently associated with both RFS and OS, and predicted outcomes are better than CA19–9 normalization alone (likelihood ratio test RFS P < 0.001, OS P = 0.01). Conclusions: This novel A-B-C-D-E classification of CA19–9 dynamics during NT was associated with postresection outcomes more precisely than CA19–9 normalization alone.

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising biomarker for patients undergoing hepatectomy for colorectal liver metastases (CLM). We hypothesized that post-hepatectomy ctDNA detection would identify patients at highest risk for early recurrence of CLM. STUDY DESIGN: Patients with CLM who underwent curative-intent hepatectomy with ctDNA analysis within 180 days postoperatively (1/2013 and 6/2020) were included. Tissue somatic mutations and ctDNA analyses were performed by next-generation sequencing panels. Survival analyses determined factors associated with clinical recurrence 1 year or earlier after hepatectomy. Patients with primary tumors in situ and without 1-year follow-up were excluded. Median follow-up was 28.3 months. RESULTS: Of 105 patients, 32 (30%) were ctDNA positive (ctDNA+) after curative-intent hepatectomy. Compared with ctDNA-negative patients, ctDNA+ patients had multiple CLM (84% vs 55%, p = 0.002) and co-mutated RAS/TP53 (47% vs 23%, p = 0.018). Multiple CLM (odds ration (OR), 5.43; p = 0.005) and co-mutated RAS/TP53 (OR, 3.30; p = 0.019) were independently associated with post-hepatectomy ctDNA. Although perioperative carcinoembryonic antigen levels were not prognostic, postoperative ctDNA+ (hazard ratio (HR), 2.04; p = 0.011) and extrahepatic disease (HR, 2.45, p = 0.004) were independently associated with worse recurrence-free survival. After adjusting for extrahepatic disease, preoperative chemotherapy, multiple CLM, tumor viability of 50% or greater, and co-mutated RAS/TP53, ctDNA+ within 180 days was the only independent risk factor for recurrence 1 year or earlier after hepatectomy (94% vs 49%; HR, 11.8; p = 0.003). CONCLUSION: Postoperative ctDNA detection is associated with early recurrence 1 year or earlier after curative-intent hepatectomy for CLM, and RAS/TP53 co-mutations result in a more than 3-fold increased risk for postoperative ctDNA positivity. This highlights the complementary effect of tumor tissue and circulating mutational profiling for patients with CLM.

The Kawaguchi–Gayet classification is a validated system to stratify open liver resections by complexity and postoperative complications. We hypothesized that Kawaguchi–Gayet classification could be used to create and implement risk-stratified posthepatectomy pathways to reduce length of stay and variation in care. Clinicopathologic data from hepatectomy patients (1/2017–6/2020) were abstracted from a prospective database. All open hepatectomies were assigned to groups based on 2 levels of Kawaguchi–Gayet classification, and corresponding risk-stratified posthepatectomy pathways were created to decrease length of stay by 1 day compared to patients who were historically treated without a pathway: low–intermediate risk (open Kawaguchi–Gayet I/II) and high risk (open Kawaguchi–Gayet III). Outcomes were compared between periods before ("PRE"; 1/1/2017–9/30/2019) and after ("POST"; 10/1/2019–6/30/2020) implementation. Among 487 open hepatectomies (PRE: 374, POST: 113), 55.0% (n = 268) were low–intermediate risk and 45.0% (n = 219) were high risk. Major complications were similar PRE/POST: low–intermediate risk (PRE: 7.8%, POST: 9.4%, P = .681) and high risk (PRE: 18.9%, POST 10.0%, P = 0.139). Risk-stratified posthepatectomy pathway implementation reduced median length of stay for both low–intermediate risk (4 to 3.5 days, P = .009) and high risk (5 to 4 days, P = 0.022) patients. Risk-stratified posthepatectomy pathways decreased length of stay variation, reflected in mean and standard deviation for all patients (PRE 5.5 ± 7.5 vs POST 4.4 ± 2.8 days). There was no difference in 90-day readmission rates between PRE (12.6%) and POST (8.8%) periods (P = .278). The creation and implementation of risk-stratified posthepatectomy pathways reduced length of stay without increasing readmissions after hepatectomy. These generalizable risk-stratified posthepatectomy pathways preoperatively stratify patients a priori into pathways for individualized preoperative discussions on realistic postoperative complications and length of stay expectations.