872P - Prognostic value of pathological intratumor heterogeneity in patients with head and neck squamous cell carcinoma treated with upfront surgery

Background

Intratumor heterogeneity (ITH) is a major cause of treatment failure in cancer. Data on ITH are scarce in head and neck squamous cell carcinoma (HNSCC). We evaluated pathological ITH (pITH) and assessed its prognostic value, along with classical prognostic parameters.

Methods

HNSCC patients treated with curative-intent primary surgery from SCANDARE (NCT03017573) were included. A pITH score (I, II, III-low and III-high) was assessed on biopsies, according to the relative contribution of poorly- and well-differentiated tumor contingents. Univariate and multivariate prognostic Cox models of recurrence-free survival (RFS) were made on pITH score and clinical (age, sex, smoking history, alcohol consumption, AJCC T- and N-stage, HPV status), pathological (differentiation, tumor-infiltrating lymphocytes [TILs], and PD-L1 combined positive score (CPS) features. We tested associations between pITH score and these parameters.

Results

A total of 88 patients were included. Most frequently tumor locations were oral cavity (51%). Most patients had low T-stage (T1-2, 59%) and HPV-negative tumor (74%). Ten patients (11%) had a I/II ITH score, 49 (56%) a III-low and 29 (33%) a III-high. Median follow-up was 17 months and median RFS was 18 months (95% CI, 14-40). In univariate analysis, the pITH score did not correlate with RFS (P = 0.6). T-stage, N-stage and TILs enrichment were associated with RFS (T3-4 vs T1-2, HR = 2.7, 95% CI, 1.4-5.3; N1-2 vs N0, HR = 1.9, 95% CI, 1.0-3.7; TILs ≥10% vs TILs <10%, HR = 0.3, 95% CI, 0.1-0.8). We found that low T-stage (T1-2) and high TILs enrichment (TILs ≥10%) were associated with a reduced risk of relapse in multivariate analysis (HR = 0.4, 95% CI, 0.2-0.9 and HR = 0.2, 95% CI, 0.04-0.5, respectively). In comparison with non-smokers, smokers had a higher proportion of tumors with I-II ITH score (19% vs 3%) and a lower proportion of tumors with III-low ITH score (48% vs 65%, adjusted P = 0.05).

Conclusions

We reported an association between pITH score and smoking history. pITH score was not found to be prognostic whereas TILs enrichment ≥10% was associated with a favorable prognosis in patients with HNSCC treated with upfront surgery. This finding is to be confirmed in an independent population.

Clinical trial identification

NCT03017573 SCANDARE.

Editorial acknowledgement

Legal entity responsible for the study

Pr Christophe Le Tourneau.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.