Somatostatin Receptor Avidity in Gastrointestinal Stromal Tumors: Theranostic Implications of Gallium-68 Scan and Eligibility for Peptide Receptor Radionuclide Therapy

Loaiza‐Bonilla, Arturo; Bonilla-Reyes, Paula A

doi:10.7759/cureus.1710

Cited by 8 publications

(8 citation statements)

References 7 publications

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“…endoscopy) for all adults with anemia. Novel imaging such as 68 Ga-DOTATATE PET/CT has high sensitivity for PGL/PCC 21 , 26 , but the sensitivity for GIST remains unclear 27 and it would likely not detect RCC. Considerations for cumulative radiation exposure and cost prohibit the regular use of 68 Ga-DOTATATE PET/CT for continuous screening; however, more data is needed to determine if it could be an effective baseline screening for individuals with SDHx variants.…”

Section: Discussionmentioning

confidence: 99%

Tumor detection rates in screening of individuals with SDHx-related hereditary paraganglioma–pheochromocytoma syndrome

Greenberg

Jacobs

Wachtel

et al. 2020

Genetics in Medicine

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Purpose: Minimal data exist regarding the efficacy of screening protocols for individuals with SDHx germline pathogenic variants with Hereditary Paraganglioma-Pheochromocytoma Syndrome. This study aimed to evaluate the SDHx -related tumor detection rate in individuals undergoing clinical screening protocols. Methods: A multi-center retrospective longitudinal observational study was conducted. Individuals with germline SDHx pathogenic variants underwent clinical whole-body imaging and biochemical testing. Results: 263 individuals with SDHx germline pathogenic variants completed 491 imaging screens. Individuals with SDHB germline pathogenic variants were most common (n=188/263, 72%), followed by SDHD ( n=35/263, 13%) and SDHC (n=28/263, 11%). SDHx -related tumors were found in 17% (n=45/263) of the cohort. Most SDHx -related tumors were identified on baseline imaging screen (n=39/46, 85%). Individuals with SDHD pathogenic variants had the highest tumor detection rate (n=14/35, 40%). Of imaging screens identifying SDHx -related paraganglioma/pheochromocytoma, 29% (n=12/41) had negative biochemical testing. Secondary actionable findings were identified in 15% (n=75/491) of imaging screens. Conclusion: Current SDHx screening protocols are effective at identifying SDHx -related tumors. Tumor detection rates vary by SDHx gene and screening has the potential to uncover actionable secondary findings. Imaging is an essential part of the screening process as biochemical testing alone does not detect all disease.

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Section: Discussionmentioning

confidence: 99%

Tumor detection rates in screening of individuals with SDHx-related hereditary paraganglioma–pheochromocytoma syndrome

Greenberg

Jacobs

Wachtel

et al. 2020

Genetics in Medicine

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“…The ability to utilise [ 68 Ga]Ga-DOTATATE PET/CT imaging as a virtual biopsy for NET is dependent on a good knowledge of the physiological uptake of [ 68 Ga]Ga-DOTATATE in normal tissue and recognising possibility of high tracer uptake in non-neuroendocrine tumours [ 29 ]. A previous case study using [ 68 Ga]Ga-DOTATATE PET/CT imaging in a patient with a suspected metastatic dSDH wtGIST demonstrated high SSTR2 tumour expression; however, this case had a synchronous parapharyngeal paraganglioma and the authors of this study rightfully acknowledged that the metastatic lesions identified on [ 68 Ga]Ga-DOTATATE PET/CT imaging may relate to the PPGL rather than wtGIST [ 18 ].…”

Section: Discussionmentioning

confidence: 94%

“…Zhao et al investigated SSTR1-5 expression in GIST using qPCR and IHC in approximately 500 tumour samples and high expression levels of both SSTR1 and SSTR2 were noted; however, details regarding the molecular classification of the GIST samples were not provided [ 15 ]. While the additional anecdotal evidence from imaging studies [ 17 , 18 ] encouraged us to pursue the possibility of a SSTR-2 targeting theragnostic strategy in this setting, the data obtained indicate that, at least in the case of wtGIST, this approach is not viable.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have reported high-level expression of the somatostatin receptor 2 (SSTR2) subtype in GIST tumours with unknown mutational status [ 15 ] and that GIST tumour sites can be identified with 111 In-Octreotide scintigraphy in 3/6 cases [ 16 ]. Recent case reports evaluating genetically profiled tumours indicate that high SSTR2 receptor overexpression can be found in KIT mutant GIST [ 17 ] as well as in dSDH wtGIST [ 18 ]. Somatostatin receptor (SSTR) PET/CT has an established role in the localisation of neuroendocrine tumours which highly express SSTR as well as a theranostic role in selecting patients for peptide receptor radionuclide therapy (PRRT) with [ 177 Lu]Lu-DOTATATE [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

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The role of [68 Ga]Ga-DOTATATE PET/CT in wild-type KIT/PDGFRA gastrointestinal stromal tumours (GIST)

et al. 2021

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Background [68 Ga]Ga-DOTATATE PET/CT is now recognised as the most sensitive functional imaging modality for the diagnosis of well-differentiated neuroendocrine tumours (NET) and can inform treatment with peptide receptor radionuclide therapy with [177Lu]Lu-DOTATATE. However, somatostatin receptor (SSTR) expression is not unique to NET, and therefore, [68 Ga]Ga-DOTATATE PET/CT may have oncological application in other tumours. Molecular profiling of gastrointestinal stromal tumours that lack activating somatic mutations in KIT or PDGFRA or so-called ‘wild-type’ GIST (wtGIST) has demonstrated that wtGIST and NET have overlapping molecular features and has encouraged exploration of shared therapeutic targets, due to a lack of effective therapies currently available for metastatic wtGIST. Aims To investigate (i) the diagnostic role of [68 Ga]Ga-DOTATATE PET/CT; and, (ii) to investigate the potential of this imaging modality to guide treatment with [177Lu]Lu-DOTATATE in patients with wtGIST. Methods [68 Ga]Ga-DOTATATE PET/CT was performed on 11 patients with confirmed or metastatic wtGIST and one patient with a history of wtGIST and a mediastinal mass suspicious for metastatic wtGIST, who was subsequently diagnosed with a metachronous mediastinal paraganglioma. Tumour expression of somatostatin receptor subtype 2 (SSTR2) using immunohistochemistry was performed on 54 tumour samples including samples from 8/12 (66.6%) patients who took part in the imaging study and 46 tumour samples from individuals not included in the imaging study. Results [68 Ga]Ga-DOTATATE PET/CT imaging was negative, demonstrating that liver metastases had lower uptake than background liver for nine cases (9/12 cases, 75%) and heterogeneous uptake of somatostatin tracer was noted for two cases (16.6%) of wtGIST. However, [68 Ga]Ga-DOTATATE PET/CT demonstrated intense tracer uptake in a synchronous paraganglioma in one case and a metachronous paraganglioma in another case with wtGIST. Conclusions Our data suggest that SSTR2 is not a diagnostic or therapeutic target in wtGIST. [68 Ga]Ga-DOTATATE PET/CT may have specific diagnostic utility in differentiating wtGIST from other primary tumours such as paraganglioma in patients with sporadic and hereditary forms of wtGIST.

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“…In considering alternative therapies for patients with TKI refractory or wild-type disease, prior in vivo work has demonstrated that GIST tumours express somatostatin receptors and bind somatostatin analogues, and therefore may respond to peptide radionuclide receptor therapy (PRRT) (20)(21)(22)(23). In 2013, Arne et al demonstrated significant expression of SSTR1 and SSTR2, with low levels of SSTR3-5 in GIST tumours via quantitative PCR.…”

Section: Introductionmentioning

confidence: 99%

Succinate dehydrogenase-deficient gastrointestinal stromal tumor: from diagnostic dilemma to novel personalised therapy in 2 case reports

Silva¹,

Rastogi²,

Chan³

et al. 2021

Transl Cancer Res TCR

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Succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST) is a unique and distinctive subtype of gastric GIST. The literature on this subtype from developing countries is exceedingly sparse. Patients with SDH-deficient GIST often experience a lack or delay in genomic profiling, despite stereotypical clinicopathologic features, potentially resulting in sub-optimal management. SDH-deficient GISTs are highly syndromic, typically have more indolent behavior, a prognosis not predicted by size and mitotic rate, a tendency to lymph node metastases, and are insensitive to standard tyrosine kinase inhibitors (TKIs). We report two women with SDH-deficient GIST. In the first case, SDH deficiency was identified late due to lack of awareness and poor access to diagnostic facilities. The patient progressed through TKI therapy, but responded to temozolomide, which is under investigation in clinical trials. In the second case, SDH deficiency was identified at diagnosis, and the patient responded well to 177 Lutetium peptide radionuclide receptor therapy (PRRT) after progressing through two lines of TKIs. We aim to highlight the need for more awareness and access to genomic diagnostic facilities for GIST patients, temozolomide as a novel therapy for SDH-deficient GIST, and the potential value of DOTATATE positron emission tomography (PET) and PRRT as a novel imaging modality and therapy for TKI insensitive GIST patients.

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Somatostatin Receptor Avidity in Gastrointestinal Stromal Tumors: Theranostic Implications of Gallium-68 Scan and Eligibility for Peptide Receptor Radionuclide Therapy

Cited by 8 publications

References 7 publications

Tumor detection rates in screening of individuals with SDHx-related hereditary paraganglioma–pheochromocytoma syndrome

Tumor detection rates in screening of individuals with SDHx-related hereditary paraganglioma–pheochromocytoma syndrome

The role of [68 Ga]Ga-DOTATATE PET/CT in wild-type KIT/PDGFRA gastrointestinal stromal tumours (GIST)

Succinate dehydrogenase-deficient gastrointestinal stromal tumor: from diagnostic dilemma to novel personalised therapy in 2 case reports

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