Abstract 701P
Background
The toxicity secondary to treatments with induction chemotherapy (ICT) with TPF (docetaxel, cisplatin and 5-fluorouracil) in head and neck squamous cell carcinoma (HNSCC) has important side effects. The standard treatment of locally advanced HNSCC is concurrent radiochemotherapy, with ICT relegated to exceptional cases. The objective of this research is to identify somatic genomic alterations associated with toxicity to TPF.
Methods
Diagnostic samples belong to the study NCT0071639122. DNA samples were processed for the identification of somatic copy number alterations (CNAs) using the OncoScan FFPEAssay. Mutational status was determined by targeted massive sequencing. The WEBbased Gene Set Analysis Toolkit was used for the functional enrichment analysis. Patients were divided into three groups (Cluster 1, complete or partial response ‘CR/PR’; Cluster 2, stable or progressive disease ‘SD/PD’; and Cluster 3, toxicity).
Results
In all, 177 patients (pts) were included (89% male/11% female). The mean age was 57.5 +/- 7 years. There were 126 pts in Cluster 1, 32 in Cluster 2 and 19 in Cluster 3. The arm-level alteration was detected in 168 pts (95%). The average number of arm-level CNA events per tumour was 15 (20 in Cluster 3). By broad CNA, in CR/PR, the most frequently alterations were 3q+ (56%) and 3p- (50%), and in SD/PD were 8q+ (59%) and 3p- (56%). Gains on 5p (74%), 8q (68%) and 3q (63%), and losses at 9p (79%), 11q (63%) and 18q (58%), were the most frequent changes in Cluster 3. CNA 5p+, 14q+ and 9p- were statistically significant (p<0.05). By focal CNAs, recurrent gains on 8p11.23 and 21q22.11 were most recurrent in Cluster 3 (12%, 17% and 42%, p<0.05) and losses on 6q21 (15%, 18% and 42%, p<0.05). The genes found in these chromosomal regions were associated with PI3K-Akt (IL7R, PTK2), DNA double strand breaks (DSBs), ATM pathway (YAP1, CHEK1) and TFG-ß pathway (ETS1, TERT).
Conclusions
This study identified several genomic regions (5p or 9p) of interest and a candidate gene associated with ICT in HNSCC. Our results suggest that genomic alterations could be used as biomarkers for therapeutic optimisation. New studies will be needed in the future.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.