Improving the Diagnosis and Management of Neuroendocrine Tumors: Utilizing New Advances in Biomarker and Molecular Imaging Science

Abstract

Neuroendocrine tumors (NET) are malignant solid tumors that arise in hormone-secreting tissue of the diffuse neuroendocrine system or endocrine glands. Although traditionally understood to be a rare disease, the incidence and prevalence of NET have increased greatly in the past 3 decades. However, during this time, progress in diagnosis and outcome of NET has generally been modest. In order to achieve improved outcome in NET, a better understanding of NET biology combined with more reliable serum markers and better techniques to identify tumor localization and small lesions are needed. Although some NET biomarkers exist, sensitive and specific markers that predict tumor growth and behavior are generally lacking. In addition, the integration of new molecular imaging technologies in patient diagnosis and follow-up has the potential to enhance care. To discuss developments and issues required to improve diagnostics and management of NET patients, with specific focus on the latest advances in molecular imaging and biomarker science, 17 global leaders in the fields of NET, molecular imaging and biomarker technology gathered to participate in a 2-day meeting hosted by Prof. Kjell Öberg at the University of Uppsala in Sweden. During this time, findings were presented regarding methods with potential prognostic and treatment applications in NET or other types of cancers. This paper describes the symposium presentations and resulting discussions.

Gene transcript analysis blood values correlate with 68Ga-DOTA-somatostatin analog (SSA) PET/CT imaging in neuroendocrine tumors and can define disease status

“…Monoanalytes, such as CgA, have been used in conjunction with clinical information to aid the interpretation of imaging with varying degrees of clinical efficacy [19,15]. Many NET patients (~30-50 %) do not have elevated CgA [43], and CgA exhibits low specific metrics with a wide variation in values depending upon the assay type, the laboratory, and numerous coexisting factors (renal insufficiency, proton pump inhibitors) [12].…”

“…An amalgamation of biomarker and imaging technologies may provide an opportunity to optimize accurate detection and early determination of disease progress [19,4]. We hypothesized that imaging and biomarkers may capture similar biological information and that combinations of this information could be of clinical utility.…”

The Status of Neuroendocrine Tumor Imaging: From Darkness to Light?

“…An informative source of information would be the integration of tumor data, such as circulating tumor cells and relevant genes, detected through mRNA measurement or circulating autoantibodies, with imaging [113]. In particular, circulating genomic data obtained from blood (tumor transcript profile or signature) at the time of imaging could be combined with morphologic or functional tumor characteristics and, thus, allow for the development of a personalized predictive assessment of tumor status before, during and after treatment [3].…”

Hematological Toxicity of Combined ¹⁷⁷Lu-Octreotate Radiopeptide Chemotherapy of Gastroenteropancreatic Neuroendocrine Tumors in Long-Term Follow-Up

“…However, a recent forum of global leaders in the field of NETs concluded that an unmet need exists for additional therapies [1]. …”

“…Short- and long-term hematological toxicity after 4 cycles of 7.8 GBq 177 Lu-DOTA-octreotate PRRT with concomitant capecitabine and temozolomide chemotherapy in our GEP NET patients was characterized and compared with published data for PRRT with 177 Lu-DOTA-octreotate [4,5,10] and 90 Y-DOTATOC [1,2], used alone or in combination [7]. The hematological toxicity of nonradioactive therapy of pancreatic NETs with somatostatin analogs [11] and the recently approved biological agents everolimus [12,13] and sunitinib [14] are also reviewed.…”