PROGNOSTIC IMPACT AND POTENTIAL PREDICTIVE ROLE OF CIRCULATING TUMOR CELLS (CTCS) AND MICROEMBOLI (CTM) IN LOCALLY ADVANCED HEAD AND NECK SQUAMOUS CELL CARCINOMA (LAHNSCC)

Introduction: The prognostic role of CTCs and CTM in locally advanced head and neck squamous cell carcinoma (LAHNSCC) is yet to be determined, with most available trials utilizing cytokeratin dependent techniques for identification and counting of CTCs. The role of induction chemotherapy (ICT) in the management of LAHNSCC is controversial, with conflicting results in the literature, and no predictive biomarkers to guide the choice of treatment strategy. The aim of this trial is to determine the prognostic impact of circulating tumor cells (CTCs) and microemboli (CTM) and its potential role as a predictor of ICT benefit in LAHNSCC. Methods: In this prospective study, peripheral blood samples of patients with non-metastatic LAHNSCC, stages III/IV, candidates for a non-surgical strategy (unresectable or organ preservation) with RT concurrent with chemotherapy (CT) or cetuximab, preceded or not by induction CT (ICT), were analyzed for CTCs and CTM before treatment, using the ISET (isolation by size of epithelial tumor cells) method. Results: Sixty-seven patients were included, 33 underwent ICT and 34 initial RT. The detection rate of baseline CTCs and CTM were 94% (63/67) and 23% (15/67) respectively. The CTCs counts were significantly correlated with survival, with an a relative increase of 20% in the risk of death (HR = 1.20; IC95%: 1.08-1.33; p < 0,001), 23% in the risk of progression (HR = 1.23; IC95%: 1.08-1.40; p = 0.004) and a reduction of 26% in the odds of complete response to treatment (OR = 0.74; CI95%: 0.58-0.95; p = 0.022) for each increase of one CTC. The presence of CTM was also correlated with worse OS (HR = 3.01; IC95%: 1.06-8.52; p = 0.029) and PFS (HR = 3.84; IC95%: 1.62-9.11; p < 0.001). High CTCs counts (cut-off 3.8/mL) and presence of CTM were potential predictors of benefit of ICT. In patients with CTCs ≤ 3,8 CTCs/mL 2y-OS was 88% for ICT versus 80% for initial RT (HR = 0.55; IC95%: 0.10-1.84; p = 0.470), while in patients with CTCs > 3.8/ mL 2y-OS was 79% for ICT versus 30% for initial RT (HR = 0.32; IC95%: 0.07-1.38; p = 0.112). The same was observed with CTM, with worse outcomes for initial RT in CTM positive patients, in comparison to the other groups (CTM positive undergoing ICT or CTM negative) both for OS (p = 0.020) and PFS (p < 0.001). Conclusions Baseline CTCs counts and presence of CTM are strongly correlated with survival and response to treatment in LAHNSCC. High CTCs counts and presence of CTM are potential predictors of ICT benefit in this population.