The prognostic and predictive value of sstr2-immunohistochemistry and sstr2-targeted imaging in neuroendocrine tumors

Brunner, Philippe; Jörg, A.; Glatz, Katharina; Bubendorf, Lukas; Radojewski, Piotr; M, Umlauft; Marincek, Nicolas; Spanjol, Petar Marko; Krause, Thomas; Dumont, Rebecca A.; Maecke, Helmut R.; Müller-Brand, Jan; Briel, Matthias; Schmitt, Anja; Perren, Aurel; Walter, Martin A.

doi:10.1007/s00259-016-3486-2

Cited by 56 publications

(50 citation statements)

References 15 publications

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“…SSTR2 expression was determined in corresponding samples. In concordance with other studies we found varying SSTR2 expression in tumour lesions among SI-NET patients [3]. SSTR2 expression did not differ solely based on tumour location.…”

Section: Discussionsupporting

confidence: 92%

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Can SSTR2 expression in previously resected SI-NETs predict overall survival after PRRT treatment of remaining lesions?

Elf

Johanson

Marin

et al. 2020

Preprint

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Purpose Small intestinal neuroendocrine tumours (SI-NET) often present with distant metastases at diagnosis. Peptide receptor radiotherapy (PRRT) with radiolabelled somatostatin analogues is a systemic treatment that increases overall survival (OS) in patients with SI-NET. However, PRRT treatment response is variable and predictive factors have not been established. PRRT predominantly targets somatostatin receptor 2 (SSTR2). This study evaluates if SSTR2 expression in SI-NET tumours predicts OS after PRRT treatment.Methods Using a previously constructed Tissue Micro Array (TMA) consisting of 412 SI-NET patients we identified a subgroup consisting of 44 patients (95 tissue samples) that had received PRRT treatment during 2006-2016 at Sahlgrenska University hospital. IHC expression of SSTR2, Ki-67 and neuroendocrine markers were assessed. A retrospective estimation of 177 Lu-DOTATATE uptake in 33 patients was performed. An additional subgroup of 34 patients with paired samples from 3 tumour sites was identified. SSTR2 expression was assessed in corresponding tissue samples (n=102). Data regarding OS and non-surgical treatment were collected for both groups.Results SSTR2 expression did not vary between tumour sites but correlated among the patients’ lesions. Patients were grouped into Low SSTR2 or High SSTR2 depending on levels of SSTR2 expression. OS based on SSTR2 expression was not significantly different. However, PRRT treated patients with low SSTR2 expression received less additional treatment compared to patients with high SSTR2 expression and had a tendency towards higher 177 Lu-DOTATATE uptake.Conclusion The results from the present study suggest that low SSTR2 expression should not exclude patients from PRRT.

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Section: Discussionsupporting

confidence: 92%

“…A high uptake on 68 Ga-DOTATATE PET has been reported to predict treatment response [13]. Some studies suggest a correlation between immunohistochemically (IHC) quantified SSTR2 expression in tissue samples and uptake in SSTR imaging with 68 Ga-DOTATATE-PET or 111 In-octreotide scintigraphy [3,10,15].…”

Section: Introductionmentioning

confidence: 99%

Can SSTR2 expression in previously resected SI-NETs predict overall survival after PRRT treatment of remaining lesions?

Elf

Johanson

Marin

et al. 2020

Preprint

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“…The association of some parameters in this dataset with PFS and OS has already been described in other papers (12,23,25,(28)(29)(30)32,35,36). However, to our knowledge, this is the first study that combines all parameters in a multivariate analysis.…”

Section: Discussionmentioning

confidence: 60%

“…Brunner et al found that SSTR type 2 expression is an independent prognostic marker for OS in 279 NET patients. A subgroup analysis of 61 patients with pancreas NET (pNET) showed that SSTR expression is not a prognostic marker for OS in pNET (12). Other nonhistologic parameters associated with survival after PRRT include gene cluster expression (13), primary tumor site (14), resection of the primary tumor (15), dominant liver metastases, and lesion size (14).…”

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confidence: 99%

Parameters to Predict Progression-Free and Overall Survival After Peptide Receptor Radionuclide Therapy: A Multivariate Analysis in 782 Patients

et al. 2019

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Peptide receptor radionuclide therapy (PRRT) is an effective treatment for patients with neuroendocrine neoplasms. The aim of this study was to identify clinical and treatment parameters associated with progression-free survival (PFS) and overall survival (OS). Methods: All patients treated from October 2002 until March 2016 at the Zentralklinik Bad Berka with at least 3 administrations of PRRT (maximal interval of 6 mo between consecutive administrations) were included. Data were collected in 5 categories: general patient characteristics, tumor characteristics, prior treatments, radioisotope used for PRRT, and blood chemistry. Survival was analyzed using Kaplan-Meier curves. Univariate and multivariate Cox regression analyses were performed to identify parameters associated with PFS and OS. Results: In total, 782 patients were included, with a median follow-up of 36 mo. The median PFS and OS were 22 and 53 mo, respectively. Parameters associated with lower PFS in the multivariate analysis were a Ki-67 of more than 5%, previous treatment with interferon-α and chemotherapy, presence of diabetes, and chromogranin-A (CgA) levels higher than 336 μg/L. Parameters associated with lower OS were a Ki-67 of more than 10%, performance status of at least 1, previous chemotherapy and ablation, and CgA levels higher than 112 μg/L. Conclusion: Higher Ki-67 values, as well as higher CgA levels and previous chemotherapy, had a negative outcome on both PFS and OS. Furthermore, PFS was negatively associated with previous interferon-α treatment and diabetes, whereas lower OS was related to prior ablation and higher performance status. http://jnm.snmjournals.org/content/60/9/1259 This article and updated information are available at: http://jnm.snmjournals.org/site/subscriptions/online.xhtml Information about subscriptions to JNM can be found at: http://jnm.snmjournals.org/site/misc/permission.xhtml

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“…As a feature of differentiation, SSTR expression may be complementary to pathology in differentiating well- from poorly differentiated grade 3 NEN. Recent evidence suggests that SSTR PET imaging results are highly correlated with SSTR-2 expression on immunohistochemistry but more accurate for predicting individual prognosis [70]. …”

Section: Prrt Requirementsmentioning

confidence: 99%

ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasms: Peptide Receptor Radionuclide Therapy with Radiolabelled Somatostatin Analogues

et al. 2017

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The purpose of these guidelines is to assist physicians caring for patients with neuroendocrine neoplasia in considering eligibility criteria for peptide receptor radionuclide therapy (PRRT) and in defining the minimum requirements for PRRT. It is not these guidelines' aim to give recommendations on the use of specific radiolabelled somatostatin analogues for PRRT as different analogues are being used, and their availability is governed by varying international regulations. However, a recent randomized controlled trial, NETTER-1, has provided evidence that may establish ¹⁷⁷Lu-DOTA-octreotate (LutaThera®) as the first widely approved agent. It also makes recommendations on what minimal patient, tumour, and treatment outcome characteristics should be reported for PRRT to facilitate robust comparisons between studies.

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The prognostic and predictive value of sstr2-immunohistochemistry and sstr2-targeted imaging in neuroendocrine tumors

Abstract: Our results suggest sstr as an independent prognostic marker in NETs. Sstr-immunohistochemistry correlates with sstr-imaging; however, sstr-imaging is more accurate for determining the individual prognosis.

Cited by 56 publications

References 15 publications

Can SSTR2 expression in previously resected SI-NETs predict overall survival after PRRT treatment of remaining lesions?

Can SSTR2 expression in previously resected SI-NETs predict overall survival after PRRT treatment of remaining lesions?

Parameters to Predict Progression-Free and Overall Survival After Peptide Receptor Radionuclide Therapy: A Multivariate Analysis in 782 Patients

ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasms: Peptide Receptor Radionuclide Therapy with Radiolabelled Somatostatin Analogues

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