ICHNO-ECHNO 2022 - Abstract Book

S93

ICHNO-ECHNO 2022

PO-0149 Immunoscore combining CD8, FoxP3 and CD68 expression and distribution predicts the prognosis of HNC

G. Descamps 1 , S. Furgiuele 2 , J.R. Lechien 3 , D. Dequanter 4 , F. Journe 2 , S. Saussez 2

1 University of Mons, Laboratory of human anatomy and experimental oncology , Mons, Belgium; 2 University of Mons, Laboratory of human anatomy and experimental oncology, Mons , Belgium; 3 Saint-Pierre Hospital , Department of Otolaryngology and Head and Neck Surgery, Brussels, Belgium; 4 Saint-Pierre Hospital, Department of Otolaryngology and Head and Neck Surgery, Brussels , Belgium Purpose or Objective The objective of this study was to assess immune cell infiltrates to develop an immunoscore for prognosis and to investigate its correlation with clinical data of patients with head and neck squamous cell carcinoma Materials and Methods CD8, FoxP3 and CD68 were evaluated by immunohistochemistry in 258 carcinoma samples and counted in stromal and intra- tumoral compartments. Optimal cut-offs were assessed to divide population regarding to survival while the prognostic value was established by using Kaplan-Meier curves and Cox regression models for each immune marker alone and in combination. Results We found with univariate analysis that infiltration of immune cells in both compartments was predictive for RFS and OS. Multivariate analysis revealed that CD8+ number influenced independently patient prognosis. Additionally, the combination of CD8, FoxP3 and CD68 in an immunoscore provided a significant association with OS (p=0.002, HR=9.87). Such immunoscore stayed significant (p=0.018, HR=11.17) in a multivariate analysis in comparison to tumour stage and histological grade which had lower prognostic values. Conclusion Altogether, our analysis indicated that an immunoscore including CD8, FoxP3 and CD68 immunostaining was a strong, independent, and significant prognostic marker which could be introduced into the landscape of current tools to improve the clinical management of head and neck cancer patients. P. Bonomo 1 , I. Desideri 1 , M. Mangoni 1 , C. Saieva 2 , C. Becherini 1 , M. Loi 1 , C. Cerbai 1 , M. Ganovelli 1 , V. Salvestrini 1 , G. Stocchi 1 , A. Palomba 3 , M. Zani 4 , L. Livi 1 1 Azienda Ospedaliero-Universitaria Careggi, Radiation Oncology, Florence, Italy; 2 Institute for cancer research, prevention and clinical network (ISPRO), Cancer Risk Factors and Lifestyle Epidemiology Unit, Florence, Italy; 3 Azienda Ospedaliero- Universitaria Careggi, Section of Pathological Anatomy, Department of Health Sciences, Florence, Italy; 4 Azienda Ospedaliero-Universitaria Careggi, Medical Physics, Florence, Italy Purpose or Objective To report on the anti-tumor activity of a novel combination consisting of Durvalumab (DUR), Cetuximab (CTX) and Radiotherapy (RT) in high-risk locally advanced head and neck squamous cell carcinoma (HNSCC). Materials and Methods DUCRO (NCT03051906) was designed as a multi-center, single-arm, phase I/II study. Patients affected by high-risk (>N2a or>T3, any N) larynx, hypopharynx and HPV negative oropharynx or HPV-positive oropharynx (>T2, >N2b, >10 pack/years; all staged with TNM/AJCC 7 th edition) were eligible. The primary endpoint of the study was 2-year progression-free survival (PFS). A safety run-in was planned. Secondary endpoints were tolerability, LRC, OS, and HRQoL. In order to avoid the potential threat of chronic locoregional lymphodepletion, a selective sparing of lymph node levels in the elective volume by keeping a mean dose below 40 Gy was outlined in the protocol. The experimental treatment consisted of IMRT (69.9 Gy/2.12 Gy in 33 fractions) with concurrent CTX (400 mg/m 2 1 week before RT start followed by 250 mg/m 2 weekly) and DUR (fixed dose of 1500 mg every 4 weeks starting from RT-CTX week 1) followed by adjuvant DUR (to a maximum of 6months after completion of RT-CTX). Due to regulatory issues which prevented from opening multiple centers, COVID-19 pandemic and DUR withdrawal from supporting company, the study was prematurely terminated in 04/21. Results Between July 2019 and August 2020, 9 patients were enrolled in the study. At diagnosis, the median age of the population was 68 years (range, 57-75). All patients were male, and the predominant primary tumor site was the oropharynx (88.8%), of whom 5/8 had HPV positive disease. The vast majority had stage IVA disease, and had significant tobacco exposure (>20 pack/years in 88.8% of them). All tumors had a PD-L1 Combined Positive Score > 1. Optimal drug exposure was observed, with mean relative dose intensity of 85.5% and 87.5% for CTX and DUR, respectively. No radiation breaks were necessary. A grade 4 mucositis lasting for 14 days corresponded to the only dose limiting toxicity we reported (figure 1: in the upper left corner, severe mucositis which persisted for 15 days prompting hospitalization and PEG placement (panel a); from the upper right corner to the bottom left, clockwise, panels b-c-d, slow healing process which occurred over one month). At a median follow-up of 11.5 months (IQR 7.7-16.7) all surviving patients (6 out of 9) are disease-free, with 1 and 2-year PFS rates of 77.7% and 58.3%, respectively. Only one patient died of disease progression. A selective sparing of node levels in the elective volume was performed in all cases, yielding a cumulative mean dose of 37.6 Gy (SD 8.4) (figure 2). Figure 1 PO-0150 Durvalumab with cetuximab and radiotherapy for locally advanced HNSCC: a phase 1/2 trial