143P - A tailored histology-driven molecular profiling algorithm proposal for salivary gland cancers

Background

Salivary gland cancers (SGC) are rare malignancies, historically divided into adenoid cystic carcinoma (AdCC) and non-AdCC, with limited systemic therapies. These two groups have different molecular profiles. This study aims to develop a tailored histology-driven molecular profiling (MP) algorithm.

Methods

This retrospective observational study was conducted at the National Cancer Institute of Milan, (referral cancer centre with focus on SGC). SGC undergoing MP from 2016 to 2023 were enrolled. Based on ASCO guidelines, the SGC cases were classified as low aggression (LA) and high aggression (HA), with AdCC considered separately. DNA and RNA analysis used next-generation sequencing (NGS) panels (≤50 or 500 genes). HER2 and Androgen receptor (AR) status were evaluated only in non-AdCC cases. Immunohistochemistry (IHC) was used for HER2 and AR, and Fluorescence in Situ Hybridization (FISH) was used for HER2. HER2 positivity was defined as 3+ at IHC or 2+ at IHC with FISH-positive. AR status was positive if >70% of tumor cells showed nuclear immunoreactivity.

Results

Totally, 253 patients were enrolled (132 AdCC, 37 LA, 84 HA). MYB/MYBL1-NFIB fusions were found in 14/21 (47%) AdCC with no druggable alterations (DA) in the fusion-positive group. DA were detected in 28/126 (22%) AdCC. In LA, ETV6-NTRK3 fusion was found in 1/10 (10%) without associated DA. DA were detected in 16/34 (47%) LA. In HA 0/19 (0%), gene fusions were found. HA harbored DA in 46/83 (55%) cases. HER 2 status was explored in 77 non-AdCC cases, mainly HA. DA were found in 0/17 (0%) cases in the HER2 + group, while in 46/77 (67%) of the HER2-negative cohort (both regardless of the AR positivity).

Conclusions

In referral centres, for AdCC, a ≤50 genes DNA panel may be considered only for MYB/MYBL1 fusion-negative cases. For LA, in NTRK fusion-negative cases at NGS RNA, a 500 genes DNA panel can be proposed. Defining the HA algorithm through HER2 status, we suggest in HER2-positive tumors, to apply a 50 genes panel. In HER2-negative cases, regardless of AR status, a 500 genes DNA panel can be advantageous. Expanding knowledge within specific histological subtypes through molecular data and saving resources makes our algorithm a clinically meaningful approach.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

S. Cavalieri: Financial Interests, Personal, Invited Speaker: Accademia Nazionale di Medicina; Financial Interests, Personal, Other, Travel expenses for invited speech at congress: MultiMed Engineers srl; Financial Interests, Personal, Other, Travel expenses for invited lecture at conference: Care Insight sas; Financial Interests, Institutional, Invited Speaker, PI of the BD4QoL randomized clinical trial (NCT05315570) conducted within the BD4QoL project, funded from the European Union’s Horizon 2020 research and innovation program under grant agreement No 875192: European Union; Non-Financial Interests, Personal, Member: AIOM, EORTC, AIOCC. G. Pruneri: Financial Interests, Personal, Invited Speaker: Roche, Lilly, Exact Sciences, Novartis; Financial Interests, Personal, Advisory Board: Exact Sciences, ADS Biotec; Financial Interests, Institutional, Invited Speaker: Illumina; Financial Interests, Institutional, Research Grant: Roche. L.F.L. Licitra: Financial Interests, Personal, Advisory Board, for expert opinion in advisory boards: AstraZeneca, Bayer, BMS, Eisai, MSD, Boehringer Ingelheim, Hoffmann-La Roche Ltd., Novartis, Roche, Debiopharm International SA, Sobi, Incyte Biosciences Italy srl, Doxa Pharma srl, Amgen, Nanobiotics, GSK, Alentis; Financial Interests, Institutional, Research Grant, Funds received by my institution for clinical studies and research activities in which I am involved: AstraZeneca, BMS, Boehringer Ingelheim, Celgene International, Eisai, Exelixis, Debiopharm International SA, Hoffmann-La Roche Ltd., IRX Therapeutics, Medpace, Merck-Serono, Merck Healthcare KGaA, MSD, Novartis, Pfizer, Roche, Adlai Nortye; Financial Interests, Institutional, Invited Speaker, Funds received by my institution for clinical studies and research activities in which I am involved: Alentis; Non-Financial Interests, Personal, Member: AIOM, ASCO, ESTRO, EORTC; Non-Financial Interests, Personal, Leadership Role: AIOCC. All other authors have declared no conflicts of interest.