Abstract 3021
Background
Intratumour heterogeneity is recognised across different tumour types and has implications for therapeutic resistance. At present, clinical practice often relies upon molecular information derived from a single biopsy of a primary or metastatic tumour. This information guides treatment choice but may not be representative of the diversity of the tumour. It is currently difficult to evaluate how effectively a single region guides treatment decisions because the formalin-fixed residual surgical sample that is not paraffin embedded for diagnostic purposes is typically thrown away. Retention and homogenisation – ‘blending’- of this residual formalin-fixed leftover tumour tissue creates a more representative sample for analysis. DNA may be extracted from this sample for sequencing. Pilot data in kidney cancer has demonstrated the potential of this methodology for robust mutational calling, accurate determination of cancer cell fraction and the ability to discern clonal from subclonal variants. Such information may be clinically relevant; for example, discerning resistant subclones prior to treatment, or identifying clonal neoantigens worth targeting with immunotherapy.
Trial design
In order to establish the feasibility of homogenization as a potential companion diagnostic tool, our study aims to 1) identify the proportion of primary tumour cases that have left over tissue amenable to homogenization across multiple tumour types and 2) pilot homogenization across multiple tumour types. The molecular profile of the homogenate will be compared to that obtained from the diagnostic specimen using next generation sequencing techniques. This is a prospective non-interventional study (NCT03832062). Patients undergoing surgical intervention at The Royal Marsden Hospital (NHS Foundation Trust) with leftover tumour tissue from primary breast, colorectal, gastric, pancreatic, ovarian, renal cancer and sarcoma surgeries, as well as melanoma lymph node dissections will be included in the feasibility assessment. We plan to homogenise 500 cases across different tumour types. The study opened in September 2018 and is expected to run for 2 years.
Clinical trial identification
NCT03832062; Release date: February 2019.
Editorial acknowledgement
Legal entity responsible for the study
Royal Marsden NHS Foundation Trust.
Funding
Ventana Medical Systems (a subsidiary of Roche).
Disclosure
L. Gallegos: Full / Part-time employment: Roche. S. Hill: Full / Part-time employment: Roche. A. Barhoumi: Full / Part-time employment: Roche. S. Stanislaw: Full / Part-time employment: Roche. M. Mendoza: Full / Part-time employment: Roche. J.M.G. Larkin: Research grant / Funding (institution): Roche; Advisory / Consultancy: Roche. N. Alexander: Full / Part-time employment: Roche; Shareholder / Stockholder / Stock options: Roche. S. Turajlic: Research grant / Funding (institution): Ventana Medical Systems (subsidiary of Roche). All other authors have declared no conflicts of interest.
Resources from the same session
4900 - Molecular profiling and prognostic significance of TP53 mutations in Diffuse Large B Cell Lymphoma: identifying a high-risk subgroup
Presenter: Yuan-Kai Shi
Session: Poster Display session 3
Resources:
Abstract
3809 - Differential expression of various miRNAs in Pediatric Cytogenetically Normal Acute Myeloid Leukemia (CN-AML)
Presenter: Vikas Gaur
Session: Poster Display session 3
Resources:
Abstract
4750 - Circulating tumour cells in head and neck and non-small cell lung cancer
Presenter: Kenneth O'Byrne
Session: Poster Display session 3
Resources:
Abstract
3704 - OX40/OX40L protein expression in Non-small cell lung cancer and its role in clinical outcome and relationships with other immune biomarkers
Presenter: Xiaoshen Zhang
Session: Poster Display session 3
Resources:
Abstract
2235 - Effect of Serum Survivin on Survival among Non-Small Cell Lung Cancer Patients; NCI Experience
Presenter: Reham Rashed
Session: Poster Display session 3
Resources:
Abstract
2788 - Enhanced performance of prognostic estimation from TCGA RNAseq data using transfer learning.
Presenter: Helene Vanacker
Session: Poster Display session 3
Resources:
Abstract
4689 - Analysis of Circulating Tumor DNA for Early Relapse Detection in Stage III Colorectal Cancer After Adjuvant Chemotherapy
Presenter: Samuel Jacobs
Session: Poster Display session 3
Resources:
Abstract
1454 - Ascites-derived circulating microRNAs as potential diagnostic biomarkers of gastric cancer-associated malignant ascites
Presenter: Hye Sook Han
Session: Poster Display session 3
Resources:
Abstract
5574 - Results from TRIO030, a Pre-Surgical Tissue-Acquisition Study to Evaluate Molecular Alterations in Human Breast Cancer Tissue Following Short-Term Exposure to the Androgen Receptor Antagonist Darolutamide
Presenter: Hsiao-Wang Chen
Session: Poster Display session 3
Resources:
Abstract
1787 - JMJD2A is a novel epigenetic factor of chemotherapeutic susceptibility in gastric cancer
Presenter: Yasushi Sato
Session: Poster Display session 3
Resources:
Abstract