Identifying an early indicator of drug efficacy in patients with metastatic colorectal cancer-a prospective evaluation of circulating tumor cells, 18F-fluorodeoxyglucose positron-emission tomography and the RECIST criteria

Ann Oncol. 2017 Jul 1;28(7):1576-1581. doi: 10.1093/annonc/mdx149.

Abstract

Background: This study investigated the predictive and prognostic significance of assessing early drug response with both positron-emission computerized tomography (PET-CT) and circulating tumor cells (CTCs) in patients receiving first-line chemotherapy for metastatic colorectal cancer.

Patients and methods: Eligible patients had PET-CT and CTC analysis at baseline and 4-6 weeks after starting chemotherapy, and then a CT scan at 10-12 weeks to assess the Response Evaluation Criteria In Solid Tumors (RECIST) response. Early response was defined as achieving a dual-endpoint consisting of PET-CT (30% drop in the sum of maximum standard uptake values-SUVmax-of target lesions) and CTC response (CTC < 3 cells/7.5 ml blood) at 4-6 weeks after starting chemotherapy.

Results: About 84 patients were enrolled with a median follow-up of 32.9 months (95% confidence interval, CI, 24.5 months-not reached, NR), and 70 patients (84.3%) completed all assessments. Achieving an early response based on the dual-endpoint was independently associated with progression-free survival (hazard ratio, HR = 0.452, 95% CI 0.267-0.765). The median progression-free survival of early responders was 7.41 months (95% CI, 6.05-9.11) compared with 5.37 months (95% CI, 4.68-6.24) in non-responders (log-rank, P = 0.0167). RECIST response at 10 weeks was independently associated with overall survival (OS) (HR = 0.484, 95% CI, 0.275-0.852). Early response based on the dual-endpoint could predict the subsequent RECIST response with a sensitivity, specificity and positive predictive value of 64%, 70% and 74%, respectively.

Conclusions: Early response based on both PET-CT and CTC analysis has prognostic and probably predictive significance in patients undergoing first-line chemotherapy for metastatic colorectal cancer. Its utility as a new tool for assessing early drug response should be further validated.

Keywords: circulating tumor cells; colorectal cancer; positron-emission tomography.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Colorectal Neoplasms / diagnostic imaging
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Disease Progression
  • Disease-Free Survival
  • Endpoint Determination
  • Female
  • Fluorodeoxyglucose F18 / administration & dosage*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multidetector Computed Tomography*
  • Neoplasm Metastasis
  • Neoplastic Cells, Circulating / pathology*
  • Positron Emission Tomography Computed Tomography / methods*
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Prospective Studies
  • Radiopharmaceuticals / administration & dosage*
  • Response Evaluation Criteria in Solid Tumors*
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18