Neuroendocrine tumor ex-vivo angiogenesis; correlation with overall survival and SUTENT sensitivity
Location
LSU Health Sciences Center - New Orleans
Event Website
https://www.medschool.lsuhsc.edu/genetics/2023_medical_student_research_poster_symposium.aspx
Presentation Date
23-10-2023 8:29 AM
Description
Introduction: Sutent, (Sunitinib) is a multiple receptor tyrosine kinases inhibitor that may affect tumor growth, angiogenesis, and metastatic progression of cancer. In the clinical NCT00428597 Sunitinib was associated with increased median progression-free survival, greater objective response rate, and fewer deaths. The purpose of the proposed study is threefold. 1) Correlate ex-vivo surrogate of NET angiogenesis with overall survival (OS) to stratify risk and improve patient selection for anti-angiogenesis intervention. 2) Quantify NET SUTENT sensitivity in to increase objective response by focusing on predicted responders. 3) Identify exceptional responders for analysis to advance new/novel therapies. METHODS: NET tumor samples, were tested using a previously published ex-vivo angiogenesis assay. Tumors were dissected into 1mm samples and cultured in thrombin-coated wells for 14 days. Endothelial cell outgrowths were quantitated as an assay for angiogenesis, percentage initiation, and growth intensity. Ex-vivo angiogenesis and OS: OS was calculated based on dates of diagnosis and dates of death extracted from medical and public records. Patients were stratified into two groups for Kaplan Meier curves. Group 1. Low angiogenesis. Angiogenesis initiation and/or growth (< average-2SEM). Group 2. High angiogenesis. Angiogenesis initiation and/or growth (> average-2SEM). NET SUTENT Sensitivity: Matched NET tumor samples were treated with 188nM SUTENT. Initiation and growth were compared to untreated tumors to calculate percentage inhibition. SUTENT exceptional responders: Were identified by three criteria. 1) Ex-vivo angiogenesis growth and initiation greater than mean-2SEM, 2) SUTENT-induced inhibition of initiation and growth >80%, and 3) SUTENT ex-vivo angiogenesis initiation and growth < mean-2SEM. RESULTS: Ex-vivo angiogenesis and OS: The 10-year survival for NET patients was 62% (N=58). In non-survivors the ex-vivo NET angiogenesis initiation and growth were greater (58.3±1.4 and 3.4±0.1 p<0.05) when compared to surviving patients (50.9±4.9, 2.6±0.36). NET tumors with low ex-vivo angiogenesis was linked to an increased OS when compared to high ex-vivo angiogenesis. SUTENT Sensitivity: Ex-vivo response to SUTENT was inconsistent. In some samples, SUTENT had no effect. In contrast, some tumors, that grew in control conditions, had 100% inhibition of sprouting. SUTENT reduced ex-vivo angiogenesis initiation and growth > 50% in 29% of tumors 3) SUTENT exceptional responders: Four tumors were identified for genomic & proteomic analysis; results are currently pending. CONCLUSIONS: Quantification of NET tumor ex-vivo angiogenesis activity has the potential to inform and improve clinical prognosis and direct personalized medicine treatment plans. In particular, the appropriateness of anti-angiogenesis treatment.
Recommended Citation
Avanzino, Kenneth C., "Neuroendocrine tumor ex-vivo angiogenesis; correlation with overall survival and SUTENT sensitivity" (2023). Medical Student Research Poster Symposium. 3.
https://digitalscholar.lsuhsc.edu/sommrd/2023MSRD/Posters/3
Neuroendocrine tumor ex-vivo angiogenesis; correlation with overall survival and SUTENT sensitivity
LSU Health Sciences Center - New Orleans
Introduction: Sutent, (Sunitinib) is a multiple receptor tyrosine kinases inhibitor that may affect tumor growth, angiogenesis, and metastatic progression of cancer. In the clinical NCT00428597 Sunitinib was associated with increased median progression-free survival, greater objective response rate, and fewer deaths. The purpose of the proposed study is threefold. 1) Correlate ex-vivo surrogate of NET angiogenesis with overall survival (OS) to stratify risk and improve patient selection for anti-angiogenesis intervention. 2) Quantify NET SUTENT sensitivity in to increase objective response by focusing on predicted responders. 3) Identify exceptional responders for analysis to advance new/novel therapies. METHODS: NET tumor samples, were tested using a previously published ex-vivo angiogenesis assay. Tumors were dissected into 1mm samples and cultured in thrombin-coated wells for 14 days. Endothelial cell outgrowths were quantitated as an assay for angiogenesis, percentage initiation, and growth intensity. Ex-vivo angiogenesis and OS: OS was calculated based on dates of diagnosis and dates of death extracted from medical and public records. Patients were stratified into two groups for Kaplan Meier curves. Group 1. Low angiogenesis. Angiogenesis initiation and/or growth (< average-2SEM). Group 2. High angiogenesis. Angiogenesis initiation and/or growth (> average-2SEM). NET SUTENT Sensitivity: Matched NET tumor samples were treated with 188nM SUTENT. Initiation and growth were compared to untreated tumors to calculate percentage inhibition. SUTENT exceptional responders: Were identified by three criteria. 1) Ex-vivo angiogenesis growth and initiation greater than mean-2SEM, 2) SUTENT-induced inhibition of initiation and growth >80%, and 3) SUTENT ex-vivo angiogenesis initiation and growth < mean-2SEM. RESULTS: Ex-vivo angiogenesis and OS: The 10-year survival for NET patients was 62% (N=58). In non-survivors the ex-vivo NET angiogenesis initiation and growth were greater (58.3±1.4 and 3.4±0.1 p<0.05) when compared to surviving patients (50.9±4.9, 2.6±0.36). NET tumors with low ex-vivo angiogenesis was linked to an increased OS when compared to high ex-vivo angiogenesis. SUTENT Sensitivity: Ex-vivo response to SUTENT was inconsistent. In some samples, SUTENT had no effect. In contrast, some tumors, that grew in control conditions, had 100% inhibition of sprouting. SUTENT reduced ex-vivo angiogenesis initiation and growth > 50% in 29% of tumors 3) SUTENT exceptional responders: Four tumors were identified for genomic & proteomic analysis; results are currently pending. CONCLUSIONS: Quantification of NET tumor ex-vivo angiogenesis activity has the potential to inform and improve clinical prognosis and direct personalized medicine treatment plans. In particular, the appropriateness of anti-angiogenesis treatment.
https://digitalscholar.lsuhsc.edu/sommrd/2023MSRD/Posters/3
Comments
Mentor: Dr. Nicholas J. Skill LSUHSC, Departments of Interdisciplinary Oncology and Surgery