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ea0098b21 | Basic Science | NANETS2023

Transcriptomic profiling of the BCL-2 pathway in Neuroendocrine Neoplasms (NENs)

Sukrithan Vineeth , Ahmed Uzair , Krause Harris , Gandhi Nishant , Walker Phillip , Lou Emil , Soares Heloisa , Vanderwalde Ari , Konda Bhavana

Background: BCL-2 is an anti-apoptotic protein associated with resistance to tumor cell death and is a histopathologic marker of neuroendocrine differentiation. We characterized the transcriptomic profile of BCL2 expression in NENs and its association with site, immune infiltration, and overall survival (OS).Methods: Next-generation sequencing of both DNA (592-gene panel or whole exome) and RNA (whole transcriptome) was performed on NENs of pancreatic (P...

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ea0098b22 | Basic Science | NANETS2023

Germline whole-exome sequencing of patients with neuroendocrine neoplasms (NENs) reveals pathogenic or likely pathogenic variants in a large subset of patients

Sukrithan Vineeth , Boateng Isaiah , Liyanarachchi Sandya , Jain Prachi , Buss Jill , Parwani Anil , Shah Manisha H. , Das Komal , Yearsely Martha , Konda Bhavana , Brock Pamela , Eisfeld Ann-Kathrin

Background: We conducted whole-exome sequencing (WES) of germline(g) and somatic(s) DNA from a prospective cohort of patients with NENs (n =151) to study the genetic predisposition to NENs.Methods: Variants obtained from gWES were filtered using a standard bio-informatics pipeline. Variant Effect Predictor (Release 107) was applied to obtain population allele frequencies. Variants were restricted to those among 974 genes obtained by combining pu...

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ea0098c7 | Clinical – Chemo/SSA/Biologics | NANETS2023

A phase II clinical trial of nivolumab and temozolomide for neuroendocrine neoplasms (NEN): updated overall survival data

Owen Dwight H. , Sukrithan Vineeth , Benner Brooke , Wei Lai , Goyal Ashima , Zhou Ye , Pilcher Carly , Curtis Nancy , Jukich Megan , Schwarz Emily , Savardekar Himanshu , Norman Ruthann , Ferguson Sarah , Kleiber Barbara , Wesolowski Robert , Carson William E. , Gregory A. Otterson III, , Verschraegen Claire F. , Shah Manisha H. , Konda Bhavana

Background: Treatment options are limited in patients with metastatic neuroendocrine neoplasms (NEN). Combination temozolomide and nivolumab showed encouraging objective response rates of 35.7% in advanced NEN regardless of site of origin, with response rates of 64% in lung NEN and 67% in pancreatic NEN (NCT03728361). We present updated survival data on follow-up from a phase II trial of combination nivolumab and temozolomide in patients with advanced NEN.<p class="abstext...

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ea0098c27 | Clinical – Nuclear Medicine/Interventional Radiology/Imaging | NANETS2023

ETCTN 10388: A first in human Phase I Trial of Triapine and Lutetium Lu 177 DOTATATE in Well-Differentiated Somatostatin Receptor-Positive Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)

Chauhan Aman , Arnold Susanne , Kolesar Jill , Carson William , Weiss Heidi , Yan Donglin , El Khouli Riham , Khurana Aman , Beumer Jan , Soares Heloisa , Mulcahy Mary , Halfdanarson Thorvardur , Li Daneng , Jacene Heather , Ivy Percy , Kohn Elise , Wright John , Rubinstein Larry , Kunos Charles , Anthony Lowell , Konda Bhavana

Background: Radiation is a potent inducer of DNA double-strand breaks, and ribonucleotide reductase (RNR) is the rate-limiting enzyme in the synthesis and repair of DNA, making RNR-targeted therapy a rationale therapeutic strategy for radiosensitization. ETCTN 10388 (NCT04234568) evaluated safety and efficacy of the combination of lutetium 177 DOTATATE, a beta-emitting radionuclide in combination with triapine, a ribonucleotide reductase (RNR) inhibitor. <p class="abstext"...

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ea0098c28 | Clinical – Nuclear Medicine/Interventional Radiology/Imaging | NANETS2023

ETCTN 10450: A phase I trial of peposertib and lutetium 177 DOTATATE in well-differentiated somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

Chauhan Aman , Kolesar Jill , Yan Donglin , Li Daneng , Khurana Aman , Edgar Carson William , Arnold Susanne M. , Gore Steven , Rubinstein Larry , Kohn Elise C. , Percy Ivy S. , Xiao Ying , Dewaraja Yuni , Soares Heloisa P. , Hendrik Beumer Jan , Konda Bhavana , Sukrithan Vineeth , Brian Anthony Lowell

Background: Radiolabeled somatostatin analogs provide a means of delivering targeted radiation with a high therapeutic index to NETs that express somatostatin receptors (SSTRs). We hypothesize that the addition of an effective radiation sensitizer could help improve the antitumor activity of Lutathera. Radiation is a potent inducer of DNA damage. The primary repair mechanism of radiation-induced double-stranded breaks (DSBs) is the nonhomologous end-joining (NHEJ) pathway, in ...

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Endocrine Abstracts

Transcriptomic profiling of the BCL-2 pathway in Neuroendocrine Neoplasms (NENs)

Germline whole-exome sequencing of patients with neuroendocrine neoplasms (NENs) reveals pathogenic or likely pathogenic variants in a large subset of patients

A phase II clinical trial of nivolumab and temozolomide for neuroendocrine neoplasms (NEN): updated overall survival data

ETCTN 10388: A first in human Phase I Trial of Triapine and Lutetium Lu 177 DOTATATE in Well-Differentiated Somatostatin Receptor-Positive Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)

ETCTN 10450: A phase I trial of peposertib and lutetium 177 DOTATATE in well-differentiated somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

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