914P - The landscape of somatic copy number alterations of head and neck squamous cell carcinoma across different anatomic sites

Background

Prognosis of head and neck squamous cell carcinomas (HNSCC) varies depending on their location. Trials such as TTCC-2007-01 have not demonstrated non-inferiority of concomitance with new treatments such as cetuximab. The aim of this study was to determine site-specific chromosomal alterations associated with response to these new treatment options.

Methods

Analysis of samples from the TTCC-2007-01 trial. Patients with LA-HNSCC treated with induction chemotherapy followed by cisplatin plus radiotherapy (Cis+RT) or cetuximab plus radiotherapy (Cet+RT). Prospective analysis of 142 patients (Cis+RT, n=72; Cet+RT, n=70). Patients were classified according to location (oral cavity, oropharynx, hypopharynx and larynx) and response to complete/partial treatment (CR/PR) and stabilisation or progression (SD/PD). DNA samples were processed with the OncoScan platform for copy number alterations (CNAs). Mutational study with TruSight targeted mass sequencing and functional analysis with WebGestalt.

Results

Oral cavity, (n=24; 16.9%), oropharynx, (n=54; 38%), larynx (n=25; 17.6%) and hypopharynx, (n= 39; 27.46%), showed similar distribution in the Cis+RT and Cet+RT groups. The patients’ mean age was 57 [29–73] years, with a predominance of males (127, 89.4%). For the Cis+RT group in hypopharynx, alterations in 1q+ and 4q- implied worse response (p<.05). Deletions in 19q11 (57.1%) and 19q13.2 (47.6%) were associated with better prognosis only in oropharynx (p<.05). Functional analysis showed involvement of the ATM response mechanism and the PIK3CA signalling pathway. In Cet+RT, gains in 2p implied non-response in oral cavity and larynx (p<.05). 2q and 7q did so significantly in oropharynx. Gene gains present on 1p36.11 (ARID1A) and 5p15.33 (TERT) were found in non-responders (p<.05). Functionally affecting the epigenetic pathway and immortalisation mechanism.

Conclusions

Distinct chromosomal alterations were identified according to location, with particular impact on epigenetic control pathways and cell immortality for oral cavity, oropharyngeal and larynx tumours treated with cetuximab. The data obtained could help to develop new biomarkers and advance towards precision medicine in HNSCC.

Clinical trial identification

TTCC-2007-01 trial (NCT0071639122). Published in year 2014.

Editorial acknowledgement

Funding

This work was supported by grants PI18/01476 from Instituto de Salud Carlos III.

Disclosure

All authors have declared no conflicts of interest.