Outcome differences of advanced larynx/hypopharynx cancer DeLOS-II trial patients related to human leukocyte antigens and haplotypes

Background PRESERVE is a joint transnational multidisciplinary project on personalized medicine in the ERA PerMed framework utilizing artificial intelligence (AI) for new signatures and models for tailored larynx organ preservation (LOP) approaches in advanced laryngeal/hypopharyngeal cancer (LHSCC).

Methods Retrospective analyses of radiomic and molecular signatures of LOP-trial patients before induction-chemo from computed tomography imaging, gene expression and mutation patterns in tumor specimens but also their genetic background, i.e. human leukocyte antigens (HLA) and haplotypes, will be used for multiscale profiling and predictive modelling to derive a multi-omic signature facilitating patient stratification before tailored LOP. Part of PRESERVE is to identify prognostic HLA traits using CareDx AlloSeq Tx17 Kits for NGS-based HLA typing.

Results Out of 52 DeLOS-II patients, 45 had sufficient amount and quality of leukocyte DNA for six-digit high-resolution typing. We confirmed the prognostic value of the HLA score from low resolution typing for 5-years progression-free survival (PFS) published before [1] regarding 10-years PFS and overall survival (OS). Additionally, superior PFS of AH8.1 carriers and inferior PFS of DR2 carriers were detected (both p≤.05).

Conclusions The genetic background of LHSCC patients predicts longtime PFS and OS after LOP. Inclusion of HLA-typing into diagnostic processes to obtain radiomic and molecular signatures before tailored LOP is intended and shall be validated within the prospective part of PRESERVE, a phase IIa feasibility trial for tailored LOP.

Funding information PRESERVE-AI for new signatures and models for tailored organ preservation approaches in laryngeal and hypopharyngeal cancer. ERA PerMed Joint Transnational Call for Proposals 2020 funded by SAB (Sächsische Aufbaubank WI413, 28.01.2022, Antragsnummer 100610496)

Publikationsverlauf

Artikel online veröffentlicht:
19. April 2024

• References

• 1 PMID: 29868484