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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

1603 - Spatial Genomic Heterogeneity from Multi-Region Endoscopic Biopsies in Primary Gastric Cancer: Implications for Precision Therapy

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Topics

Pathology/Molecular Biology

Tumour Site

Gastric Cancer

Presenters

Samuel Klempner

Citation

Annals of Oncology (2018) 29 (suppl_8): viii205-viii270. 10.1093/annonc/mdy282

Authors

S.J. Klempner1, J. Chao2, K. Kim3, K. Kim4, S. Kim3, J. Lee3, H. Lee5

Author affiliations

  • 1 Medical Oncology, The Angeles Clinic and Research Institute, 90025 - Los Angeles/US
  • 2 Department Of Medical Oncology And Therapeutics, City of Hope, 91010 - Duarte/US
  • 3 Medicine, Samsung Medical Center, Seoul/KR
  • 4 Pathology, Samsung Medical Center, Seoul/KR
  • 5 Gastroenterology, Samsung Medical Center, Seoul/KR
More

Resources

Abstract 1603

Background

The responses and benefit from targeted therapies in gastric cancer (GC) remain limited and improved biologic understanding is needed. Both inter-tumoral and intra-tumoral heterogeneity for HER2 and EGFR has been observed in small datasets and may limit efficacy of targeted therapies. Broader heterogeneity assessment has not been studied. We sought to explore intra-tumoral heterogeneity in GC by multi-region sampling of primary gastric tumors with subsequent interrogation of mutational differences via next generation sequencing (NGS) and cell-free DNA (cfDNA) analyses.

Methods

Patients with newly diagnosed advanced GC underwent endoscopic mapping and pre-determined 8-region biopsy of the primary with concurrent plasma cfDNA sampling. Biopsy samples were subjected to NGS using a 32-gene custom panel and plasma cfDNA analyzed via 28-gene cfDNA assay. Clinicopathologic features and genomic alterations (GA) were abstracted and descriptive statistics were used to compare samples.

Results

All six initial patients underwent multi-region biopsy and NGS. Within a given patient the average number of GA observed in all biopsies (shared GA) was 3.3 with an average of 12.8 non-shared alterations (p = < 0.05). There was no significant difference in the average mutant allele frequency (MAF) or MAF variability between shared and non-shared GA in the primary tumor (p = > 0.05). Cell free DNA analyses identified GA not found in each respective case’s multi-region primary tumor analysis, likely reflective of GA derived from metastatic sites. An updated cohort will be presented.

Conclusions

Endoscopic multi-region biopsy of GC is feasible and significant genomic heterogeneity existed within the primary in all patients. Paired cfDNA analyses should also be included to complement studies of intra-tumoral heterogeneity. Standardized methods to determine intra and inter-tumoral heterogeneity are needed and stratification by heterogeneity score in prospective trials may inform optimal patient selection, particularly in targeted therapies.

Clinical trial identification

Legal entity responsible for the study

Samsung Medical Center.

Funding

Samsung Medical Center.

Editorial Acknowledgement

Disclosure

S.J. Klempner: Consulting, Advisory: Lilly Oncology, Boston Biomedical, Astellas, Merck. J. Chao: Consulting, Advisory: Boston Biomedical, Merck, Five Prime Therapeutics. All other authors have declared no conflicts of interest.

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