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.
Resources from the same session
1310 - Lymphocytes express receptor tyrosine kinases in patients with renal cell carcinoma and healthy donors
Presenter: Ilya Tsimafeyeu
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
Resources:
Abstract
1596 - Oncogenes analysis using GO-based clustering
Presenter: Dmitriy Babenko
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
Resources:
Abstract
5181 - PNU-74654 enhances the antiproliferative effects of 5-FU in breast cancer and antagonizes thrombin induced cell growth via the Wnt Pathway
Presenter: Soodabeh Shahid Sales
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
Resources:
Abstract
3344 - P21 has the potential to become the monitoring marker for the CDK4/6 inhibitors resistance in breast cancer
Presenter: Masafumi Iida
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
Resources:
Abstract
894 - Overexpression of NAMPT in adult T-cell leukemia/lymphoma patients and anti-tumor activity of a NAMPT inhibitor in vivo
Presenter: Tomohiro Kozako
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
Resources:
Abstract
2224 - 9-ING-41, a clinically relevant inhibitor of Glycogen Synthase Kinase-3 (GSK-3), is active pre-clinically in human bladder and renal cell cancers
Presenter: Hiroo Kuroki
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
Resources:
Abstract
3380 - A new natural compound identified with metabolomic approach has cytotoxic activity against human colorectal cancer cell lines with acquired resistance to cetuximab
Presenter: Vincenzo De Falco
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
Resources:
Abstract
4713 - Multiple Myeloma Metal Levels and Proteasome Activity
Presenter: Kai Uwe Stumpf
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
Resources:
Abstract
4134 - A translational drug-screening tool for interrogating the effect of anti-TGF-_ therapy on fibroblast activity and the desmoplastic reaction
Presenter: Neel Nissen
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
Resources:
Abstract
2736 - Eribulin demonstrate selectively high sensitivity to recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) cells and xenograft tumors
Presenter: hiroko kitahara
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
Resources:
Abstract