Circulating tumor cells detected in follow-up predict survival outcomes in tri-modality management of advanced non-metastatic esophageal cancer: a secondary analysis of the QUINTETT randomized trial

Edward Yu; Alison L Allan; Michael Sanatani; Debra Lewis; Andrew Warner; A Rashid Dar; Brian P Yaremko; Lori E Lowes; David A Palma; Jacques Raphael; Mark D Vincent; George B Rodrigues; Dalilah Fortin; Richard I Inculet; Eric Frechette; Joel Bierer; Jeffery Law; Jawaid Younus; Richard A Malthaner

doi:10.1186/s12885-022-09846-0

Circulating tumor cells detected in follow-up predict survival outcomes in tri-modality management of advanced non-metastatic esophageal cancer: a secondary analysis of the QUINTETT randomized trial

BMC Cancer. 2022 Jul 8;22(1):746. doi: 10.1186/s12885-022-09846-0.

Authors

Edward Yu¹, Alison L Allan², Michael Sanatani³, Debra Lewis⁴, Andrew Warner⁵, A Rashid Dar⁵, Brian P Yaremko⁵, Lori E Lowes⁶, David A Palma⁵, Jacques Raphael³, Mark D Vincent³, George B Rodrigues⁵, Dalilah Fortin⁴, Richard I Inculet⁴, Eric Frechette⁷, Joel Bierer⁸, Jeffery Law⁸, Jawaid Younus³, Richard A Malthaner⁴

Affiliations

¹ Department of Oncology, Divisions of Radiation Oncology, Western University, 1151 Richmond Street, London, Ontario, N6A3K7, Canada. eyu@uwo.ca.
² Experimental Oncology, London, Ontario, Canada.
³ Medical Oncology, London, Ontario, Canada.
⁴ Thoracic Surgery and Surgical Oncology, London, Ontario, Canada.
⁵ Department of Oncology, Divisions of Radiation Oncology, Western University, 1151 Richmond Street, London, Ontario, N6A3K7, Canada.
⁶ Pathology & laboratory medicine, London Health Science Centre, London, Ontario, Canada.
⁷ Department of Thoracic Surgery and Surgical Oncology, Sherbrooke University, Sherbrooke, Quebec, Canada.
⁸ Department of Medicine, Western University, London, Ontario, Canada.

Abstract

Background: Our aim was to establish if presence of circulating tumor cells (CTCs) predicted worse outcome in patients with non-metastatic esophageal cancer undergoing tri-modality therapy.

Methods: We prospectively collected CTC data from patients with operable non-metastatic esophageal cancer from April 2009 to November 2016 enrolled in our QUINTETT esophageal cancer randomized trial (NCT00907543). Patients were randomized to receive either neoadjuvant cisplatin and 5-fluorouracil (5-FU) plus radiotherapy followed by surgical resection (Neoadjuvant) or adjuvant cisplatin, 5-FU, and epirubicin chemotherapy with concurrent extended volume radiotherapy following surgical resection (Adjuvant). CTCs were identified with the CellSearch® system before the initiation of any treatment (surgery or chemoradiotherapy) as well as at 6-, 12-, and 24-months post-treatment. The threshold for CTC positivity was one and the findings were correlated with patient prognosis.

Results: CTC data were available for 74 of 96 patients and identified in 27 patients (36.5%) at a median follow-up of 13.1months (interquartile range:6.8-24.1 months). Detection of CTCs at any follow-up visit was significantly predictive of worse disease-free survival (DFS;hazard ratio [HR]: 2.44; 95% confidence interval [CI]: 1.41-4.24; p=0.002), regional control (HR: 6.18; 95% CI: 1.18-32.35; p=0.031), distant control (HR: 2.93; 95% CI: 1.52-5.65;p=0.001) and overall survival (OS;HR: 2.02; 95% CI: 1.16-3.51; p=0.013). After adjusting for receiving neoadjuvant vs. adjuvant chemoradiotherapy, the presence of CTCs at any follow-up visit remained significantly predictive of worse OS ([HR]:2.02;95% [Cl]:1.16-3.51; p=0.013) and DFS (HR: 2.49;95% Cl: 1.43-4.33; p=0.001). Similarly, any observed increase in CTCs was significantly predictive of worse OS (HR: 3.14; 95% CI: 1.56-6.34; p=0.001) and DFS (HR: 3.34; 95% CI: 1.67-6.69; p<0.001).

Conclusion: The presence of CTCs in patients during follow-up after tri-modality therapy was associated with significantly poorer DFS and OS regardless of timing of chemoradiotherapy.

Keywords: Circulating tumor cells; Esophageal cancer; Non-metastatic; Prognostic.

Publication types

Randomized Controlled Trial

MeSH terms

Cisplatin / therapeutic use
Esophageal Neoplasms* / drug therapy
Fluorouracil / therapeutic use
Follow-Up Studies
Humans
Neoplastic Cells, Circulating* / pathology
Prognosis

Substances

Cisplatin
Fluorouracil