Characterization of an oligometastatic state in patients with metastatic pancreatic adenocarcinoma undergoing systemic chemotherapy

Cancer Med. 2024 Jan;13(1):e6582. doi: 10.1002/cam4.6582. Epub 2023 Dec 22.

Abstract

Purpose/objectives: Most patients with pancreatic adenocarcinoma (PDAC) will present with distant metastatic disease at diagnosis. We sought to identify clinical characteristics associated with prolonged overall survival (OS) in patients presenting with metastatic PDAC.

Materials/methods: Patients presenting with metastatic PDAC that received treatment at our institution with FOLFIRINOX or gemcitabine-based chemotherapies between August 1, 2011 and September 1, 2017 were included in the study. Metastatic disease burden was comprehensively characterized radiologically via individual diagnostic imaging segmentation. Landmark analysis was performed at 18 months, and survival curves were estimated using the Kaplan-Meier method and compared between groups via the log-rank test. ECOG and Charlson Comorbidity Index (CCI) were calculated for all patients.

Results: 121 patients were included with a median age of 62 years (37-86), 40% were female, 25% had ECOG 0 at presentation. Of the 121 patients included, 33% (n = 41) were alive at 12 months and 25% (n = 31) were alive at 18 months. Landmark analysis demonstrated a significant difference between patients surviving <18 months and ≥18 months regarding the presence of lung only metastases (36% vs. 16%, p = 0.04), number of organs with metastases (≥2 vs. 1, p = 0.04), and disease volume (mean of 19.1 cc vs. 1.4 cc, p = 0.04). At Year 1, predictors for improved OS included ECOG status at diagnosis (ECOG 0 vs. ECOG 1, p = 0.04), metastatic disease volume at diagnosis (≤0.1 cc vs. >60 cc, p = 0.004), metastasis only in the liver (p = 0.04), and normalization of CA 19-9 (p < 0.001). At Year 2, the only predictor of improved OS was normalization of the CA 19-9 (p = 0.03). In those patients that normalized their CA 19-9, median overall survival was 16 months.

Conclusions: In this exploratory analysis normalization of CA-19-9 or volumetric metastatic disease burden less than 0.2 cc demonstrated a remarkable OS, similar to that of patients with non-metastatic disease. These metrics are useful for counseling patients and identifying cohorts that may be optimal for trials exploring metastatic and/or local tumor-directed interventions.

Keywords: neoplasm metastasis; oligometastasis; pancreatic neoplasms.

MeSH terms

  • Adenocarcinoma* / drug therapy
  • Adenocarcinoma* / mortality
  • Adenocarcinoma* / secondary
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Female
  • Fluorouracil* / administration & dosage
  • Fluorouracil* / therapeutic use
  • Gemcitabine
  • Humans
  • Irinotecan / administration & dosage
  • Irinotecan / therapeutic use
  • Kaplan-Meier Estimate
  • Leucovorin* / administration & dosage
  • Leucovorin* / therapeutic use
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lung Neoplasms / secondary
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Oxaliplatin / administration & dosage
  • Oxaliplatin / therapeutic use
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / mortality
  • Pancreatic Neoplasms* / pathology
  • Prognosis
  • Retrospective Studies

Substances

  • Leucovorin
  • Fluorouracil
  • folfirinox
  • Deoxycytidine
  • Gemcitabine
  • Irinotecan
  • Oxaliplatin