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Somatostatin Receptor 2 Expression Profiles and Their Correlation with the Efficacy of Somatostatin Analogues in Gastrointestinal Neuroendocrine Tumors.

ABSTRACT: Somatostatin analogues (SSAs) are widely used to treat gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Somatostatin receptor 2 (SSTR2) immunoreactivity serves as a predictive marker of the therapeutic efficacy of SSAs in pancreatic NETs. However, SSTR2 expression profiles in tumor cells and their association with the therapeutic efficacy of SSAs remains virtually unknown in gastrointestinal NETs (GI-NETs). Therefore, we evaluated the association between SSTR2 immunoreactivity and embryological origin and proliferative activity in 132 resected surgical tissues of GI-NETs. The correlation between SSAs' therapeutic efficacy and SSTR2 immunoreactivity was evaluated in 14 GI-NETs treated with SSAs. SSTR2 immunoreactivity was evaluated using Volante scores, immunoreactive scores, and digital image analysis (DIA). SSTR2 immunoreactivity was significantly negatively and positively correlated with the Ki-67 labeling index in foregut and hindgut NETs, respectively. In the normal mucosa, neuroendocrine cells in the rectum had significantly lower positive rates of SSTR2 than those in the stomach and duodenum. SSTR2 expression profiles in GI-NETs could differ by primary sites, while the difference of those between foregut and hindgut NETs might be derived from the SSTR2 status of normal neuroendocrine cell counterparts. In addition, DIA could provide a good alternative for predicting response to SSAs in evaluating SSTR2 immunoreactivity of GI-NETs.

SUBMITTER: Watanabe H

PROVIDER: S-EPMC8834049 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Somatostatin Receptor 2 Expression Profiles and Their Correlation with the Efficacy of Somatostatin Analogues in Gastrointestinal Neuroendocrine Tumors.

Watanabe Hirofumi H Fujishima Fumiyoshi F Komoto Izumi I Imamura Masayuki M Hijioka Susumu S Hara Kazuo K Yatabe Yasushi Y Kudo Atsushi A Masui Toshihiko T Tsuchikawa Takahiro T Sakamoto Kazuhiro K Shiga Hisashi H Nakamura Tomohiro T Nakaya Naoki N Motoi Fuyuhiko F Unno Michiaki M Sasano Hironobu H

Cancers 20220202 3

Somatostatin analogues (SSAs) are widely used to treat gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Somatostatin receptor 2 (SSTR2) immunoreactivity serves as a predictive marker of the therapeutic efficacy of SSAs in pancreatic NETs. However, SSTR2 expression profiles in tumor cells and their association with the therapeutic efficacy of SSAs remains virtually unknown in gastrointestinal NETs (GI-NETs). Therefore, we evaluated the association between SSTR2 immunoreactivity and embryo ...[more]

PMID: 35159042

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Project description:In recent decades, the incidence of neuroendocrine tumors (NETs) has steadily increased. Due to the slow-growing nature of these tumors and the lack of early symptoms, most cases are diagnosed at advanced stages, when curative treatment options are no longer available. Prognosis and survival of patients with NETs are determined by the location of the primary lesion, biochemical functional status, differentiation, initial staging, and response to treatment. Somatostatin analogue (SSA) therapy has been a mainstay of antisecretory therapy in functioning neuroendocrine tumors, which cause various clinical symptoms depending on hormonal hypersecretion. Beyond symptomatic management, recent research demonstrates that SSAs exert antiproliferative effects and inhibit tumor growth via the somatostatin receptor 2 (SSTR2). Both the PROMID (placebo-controlled, prospective, randomized study in patients with metastatic neuroendocrine midgut tumors) and the CLARINET (controlled study of lanreotide antiproliferative response in neuroendocrine tumors) trial showed a statistically significant prolongation of time to progression/progression-free survival (TTP/PFS) upon SSA treatment, compared to placebo. Moreover, the combination of SSA with peptide receptor radionuclide therapy (PRRT) in small intestinal NETs has proven efficacy in the phase 3 neuroendocrine tumours therapy (NETTER 1) trial. PRRT is currently being tested for enteropancreatic NETs versus everolimus in the COMPETE trial, and the potential of SSTR-antagonists in PRRT is now being evaluated in early phase I/II clinical trials. This review provides a synopsis on the pharmacological development of SSAs and their use as antisecretory drugs. Moreover, this review highlights the clinical evidence of SSAs in monotherapy, and in combination with other treatment modalities, as applied to the antiproliferative management of neuroendocrine tumors with special attention to recent high-quality phase III trials.

Project description:PurposeEvaluate patients' and nurses' experiences, including injection problem frequency, with the somatostatin analogues (SSAs) lanreotide autogel® (Somatuline® autogel®, deep subcutaneous) and octreotide long-acting release (LAR) (Sandostatin® LAR®, intramuscular) when treating gastroenteropancreatic neuroendocrine tumors (GEP-NETs).MethodsAn observational, cross-sectional study across 2 NET centers in Sweden. Questionnaires based on participants' most recent injection experience were sent to patients with GEP-NETs treated with octreotide or lanreotide, and to nurses administering these treatments. Nurses were identified via patients completing their questionnaires. Resource use was sourced from Swedish prescription registry records. The planned sample size was 200, based on an estimated proportion of 0.50 and ±7% precision.Results119/156 patients (n=53, lanreotide; n=66, octreotide) and 43/53 nurses (n=22, lanreotide; n=21, octreotide) completed questionnaires. Despite smaller recruitment than planned, the endpoint precision was ±9% with 119 participants, and still considered reasonable. More octreotide-treated patients reported problems (18% vs none; P=0.001) and experienced moderate-to-high anxiety pre-injection (11% vs 2%). Patients had similar physical HRQoL scores overall (Short Form-12 mean composite scores: physical: 39.4 vs 37.6; mental: 50.7 vs 49.6). The mean number of lanreotide and octreotide doses dispensed per year were 11.1 and 12.6, respectively (P<0.05). In the lanreotide group, 28% self-injected, while 29% were not aware they could self-inject. In the octreotide group, 3% self-injected and 73% were unaware of the availability of an SSA for self-injection. Most patients (61%) felt well-informed about their disease and treatment. Nurses were generally experienced and felt confident and well-informed about giving SSA injections; however, only 12% felt well-informed about the disease and treatment.ConclusionThose treated with lanreotide reported fewer injection problems and experienced less pre-injection anxiety than those treated with octreotide. SSA choice did not appear to affect patients' HRQoL. Some patients treated with octreotide were unaware of an SSA with the flexibility of self-injection.

Dataset Information

Somatostatin Receptor 2 Expression Profiles and Their Correlation with the Efficacy of Somatostatin Analogues in Gastrointestinal Neuroendocrine Tumors.

Publications

Somatostatin Receptor 2 Expression Profiles and Their Correlation with the Efficacy of Somatostatin Analogues in Gastrointestinal Neuroendocrine Tumors.

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