Abstract 113P
Background
Neuroendocrine neoplasms are a heterogeneous class of rare tumours accounting for ∼2% of all malignancies. Despite they primarily arise from neuroendocrine cells, some of the more common adenocarcinomas can transform into NECs (Neuroendocrine cancers) under the pressure of anticancer treatments. Identification of transformed NEC (tNEC) is challenged by the poor feasibility of tissue biopsies. Genome alterations such as RB1loss and TP53 mutation are typically co-associated within NECs and testing via liquid biopsy could represent a valid approach to detect tNECs years after the original histology.
Methods
Blood samples (≤60 mL) were collected from patients with solid tumours within the TARGET National study (NCT04723316). As per study protocol, circulating tumour DNA (ctDNA) was sequenced using Foundation Medicine Liquid CDx assay. Subsequently, patients consented at Newcastle Hospitals were identified on the TARGET National database.
Results
We recruited 612 patients; out of them, 35/612 (5.7%) tumours harboured RB1 and TP53 gene co-alteration. Of these, 15 (42.8%) were lung cancers, 5 (14.3%) prostate cancers, 5 (14.3%) breast cancers, 4 (11.4%) bladder cancers, 2 (5.7%) colon cancer, 2 (5.7%) oesophagus carcinomas, 1 (2.9%) liver and 1 (2.9%) adrenocortical carcinoma. The majority of TP53 mutation were point mutations (62.9%). Differenly, for RB1 14 (40%) were frameshift mutations, 12 (34.3%) mutations leading to stop codons, 5 (14.3%) splice site mutations, 3 (8.6%) point mutations, and 1 (2.9%) an intron rearrangement. At the time of original diagnosis, 12/35 (34.3%) patients had histological evidence of NEC, while the remaining 23 (65.7%) started as histologically confirmed adenocarcinomas. The time from diagnosis to testing for TARGET was 27.0 mos for tNECs and 15.8 mos for primary NECs, while overall survival from TARGET was 5.6 and 7.2 mos, respectively.
Conclusions
Our research shows that ctDNA analyses can reliably detect RB1 and TP53 co-mutation in a wide range of cancers without the constraints of a tissue biopsy, identifying both NECs and tNECs. Interestingly, while cancers originally identified as adenocarcinomas have a better outcome compared to NEC, their OS is comparable upon NE transformation.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
C. Oing: Financial Interests, Personal, Invited Speaker, Renal Cancer Expert Panel Case Presentation: Ipsen; Financial Interests, Personal, Invited Speaker, Talk on Pain Management in GU Cancer Patients: Medac; Financial Interests, Personal, Invited Speaker, Case Presentation Soft Tissue Sarcoma: Roche; Financial Interests, Personal, Advisory Board, Ad Board on discussing novel educational events for young haematologists: Novartis; Financial Interests, Personal, Invited Speaker, Science Slam with a presentation on young professional support from oncological societies in Germany: AstraZeneca; Financial Interests, Personal, Advisory Board, AdBoard assessing educational needs for oncology professionals regarding G-CSF use: Sandoz; Financial Interests, Personal, Invited Speaker, Presentation on Burnout and Resilience in medical oncology professionals: Asklepios Hamburg; Financial Interests, Personal, Advisory Board, Larotrectinib use in sarcoma: Bayer; Financial Interests, Personal, Advisory Board, Experiences with Cabo/Nivo as first-line treatment for metastatic RCC: Ipsen; Financial Interests, Personal, Advisory Board, Workshop series on improving customer experience: Pfizer; Non-Financial Interests, Personal, Other, Clinical Advisory role in early drug discovery with a fellowship position affiliated with Astex Pharmaceuticals, Cambridge, UK: Astex Pharmaceuticals; Non-Financial Interests, Institutional, Product Samples, Cytotoxic Agent for Preclinical Experiments: PharmaMar. R. Plummer: Financial Interests, Personal, Advisory Board: Pierre Faber, Bayer, Novartis, BMS, Cybrexa, Ellipses, CV6 Therapeutics, Astex Therapetics, Sanofi Aventis, Immunocore, Genmab, Medivir, Onexo, Incyte; Financial Interests, Institutional, Royalties, Royalties relating to rucaparib licencing: Clovis Oncology; Financial Interests, Personal, Other, Honorarium as member of IDMC: SOTIO, Alligator Biosciences, AstraZeneca; Financial Interests, Personal, Other, Honoraria as member of IDMC: GSK. A. Greystoke: Financial Interests, Personal, Advisory Board: BMS, AstraZeneca, Boehringer Ingelheim, Takeda, Roche, Novartis; Financial Interests, Personal, Invited Speaker: Merck, MSD, Pfizer, Janssen; Financial Interests, Institutional, Invited Speaker: MSD, Pfizer, AstraZeneca, Novartis, Achilles; Non-Financial Interests, Personal, Advisory Role: National Institute for Health and Clinical Excellence; Non-Financial Interests, Personal, Leadership Role, Steering Committee member: British Thoracic Oncology Group; Other, Personal, Other, Clinical Lead for Cancer (paid position): North East England and Yorkshire Genomic Laboratory Hub. P. Rescigno: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Janssen, Pfizer, Merck, MSD Italy, Bayer, Ibsen. All other authors have declared no conflicts of interest.