Circulating Tumor Cell Detection during Neoadjuvant Chemotherapy to Predict Early Response in Locally Advanced Oropharyngeal Cancers: A Prospective Pilot Study.

Arnaud Gauthier,Pierre Philouze,Gersende Alphonse,Philippe Céruse,Anne-Sophie Wozny,Dominique Ardail,Léa Payen,Alexandra Lauret,Céline Malesys,Claire Rodriguez-Lafrasse

doi:10.3390/jpm12030445

Abstract

Patients with locally advanced oropharyngeal carcinoma treated with neoadjuvant chemotherapy are reassessed both radiologically and clinically to adapt their treatment after the first cycle. However, some responders show early tumor progression after adjuvant radiotherapy. This cohort study evaluated circulating tumor cells (CTCs) from a population of locally advanced oropharyngeal carcinoma patients treated with docetaxel, cisplatin, and 5-fluorouracil (DCF) induction chemotherapy or DCF with a modified dose and fractioned administration. The counts and phenotypes of CTCs were assessed at baseline and at day 21 of treatment, after isolation using the RosetteSepTM technique based on negative enrichment. At baseline, 6 out of 21 patients had CTCs (28.6%). On day 21, 5 out of 11 patients had CTCs (41.6%). There was no significant difference in the overall and progression-free survival between patients with or without CTCs at baseline (p = 0.44 and 0.78) or day 21 (p = 0.88 and 0.5). Out of the 11 patients tested at day 21, 4 had a positive variation of CTCs (33%). Patients with a positive variation of CTCs display a lower overall survival. Our findings suggest that the variation in the number of CTCs would be a better guide to the management of treatment, with possible early changes in treatment strategy.

Highlights

Head and neck squamous cell cancer (HNSCC) is the sixth most common cancer worldwide [1]
No significant associations were observed between the number of Circulating tumor cells (CTCs) at baseline and clinical characteristics of the patients, including sex, age, clinical stage, tobacco use, alcohol intake, and human papillomavirus status (Table 1)
On day 21, before the second course of DCF treatment, CTCs were collected from patients who received DCF chemotherapy, as well as from 1 patient who received mDCF

Summary

Introduction

Head and neck squamous cell cancer (HNSCC) is the sixth most common cancer worldwide [1]. Current therapeutic strategies are multimodal and use either a combination of surgery followed by radiochemotherapy, neoadjuvant chemotherapy followed by radiotherapy, or radiochemotherapy, depending on the tumor location and stage. These strategies have not demonstrated any superiority to date, and locoregional recurrences and/or metastases lead to therapeutic failure with a less than 50% overall survival (OS). Circulating tumor cells (CTCs) represent a heterogeneous population with wide plasticity and include epithelial cancer cells, cells in the process of epithelial-to-mesenchymal transition, mesenchymal cells, and cancer stem cells (CSCs). CSCs are demonstrated to be responsible for self-renewal and tumor growth in HNSCC [3,4]. The number of circulating CTCs is correlated with poor prognoses in lung, colorectal, prostate, and breast cancers [5–9]

Methods

Results

Discussion

Conclusion