⁶⁸Ga-DOTATOC Imaging of Neuroendocrine Tumors: A Systematic Review and Metaanalysis

Abstract

Ga-DOTATOC, a somatostatin receptor-targeted ligand, has been used clinically in Europe over the past decade for imaging neuroendocrine tumors (NETs). It appears to be quite sensitive and effective for clinical management decision making. This metaanalysis summarizes the efficacy of Ga-DOTATOC for several distinct indications and is intended to support approval of this agent by the U.S. Food and Drug Administration. The major electronic medical databases were searched for relevant papers over the period from January 2001 to November 2015. Papers were selected for review in 3 categories: clinical trials that reported sensitivity and specificity, comparison studies with In-octreotide, and change of management studies. All the eligible papers underwent Quality Assessment of Diagnostic Accuracy Studies (QUADAS) assessment, which was useful in the final selection of papers for review. The initial search yielded 468 papers. After detailed evaluation, 17 papers were finally selected. Five types of studies emerged: workup of patients with symptoms and biomarker findings suggestive of NET, but with negative conventional imaging (3 papers, yield was only 13%); sensitivity (12 papers; sensitivity, 92%) and specificity (7 papers; specificity, 82%); identification of site of unknown primary in patients with metastatic NET (4 papers, yield was 44%); impact on subsequent NET patient management (4 papers, change in management in 51%); and comparison with In-octreotide (2 papers, sensitivity of DOTATOC on a per-lesion basis was 100%, forIn-octreotide it was 78.2%; specificity was not available). Safety was not explicitly addressed in any study, but there were no reports of adverse events. Ga-DOTATOC is useful for evaluating the presence and extent in disease for staging and restaging and for assisting in treatment decision making for patients with NET. It is also effective in locating the site of an unknown primary in NET patients who present with metastatic NET, but no known primary tumor. It also appears to be more accurate thanIn-octreotide. Although Ga-DOTATOC would seem to be useful in evaluating patients with suggestive symptoms and biomarker findings, it does not perform well in this setting and has low yield. Overall, it appears to be an excellent imaging agent to assess patients with known NET and frequently leads to a change in management.

Prospective evaluation of 68Ga‐DOTATATE PET/CT in limited disease neuroendocrine tumours and/or elevated serum neuroendocrine biomarkers

“…18 F‐FDOPA PET/CT performed better than SRS and CT of midgut NETs but may have suboptimal sensitivity in some pancreatic NETs . Several studies have shown that 68 Ga‐DOTA‐SSAs like 68 Ga‐DOTATATE, 68 Ga‐DOTATOC and 68 Ga‐DOTANOC have a high detection rate and a high impact on patient management, especially in NETs with unknown primary or in potential candidates for curative surgery or requiring liver transplantation.…”

Ovarian metastases from ileal neuroendocrine tumour: Multimodality imaging

“…68‐Gallium DOTATOC PET‐CT is also a powerful tool in the management of patients with NET, for evaluating the presence and extent of the disease and to assist in treatment decision‐making …”

Appropriate Use Criteria for Somatostatin Receptor PET Imaging in Neuroendocrine Tumors

“…This indication resulted in significant disagreement within the workgroup. On the one hand, the overall yield of finding a NET in this patient population is low, and SSTR PET may also result in false-positives that could lead to unnecessary additional tests or procedures (12). However, in such a situation, a negative SSTR PET result may play an important role, as it could end the diagnostic workup, resulting in a more cost-effective evaluation.…”

“…No adverse events have been reported in association with the administration of SSTR PET agents (12).…”

“…The primary purpose of the systematic review was to assess the diagnostic accuracy and comparative effectiveness of SSTR PET in patients with NETs. Two additional metaanalyses were also included in the process (12,32). The key research questions used to guide the systematic review were as follows: What is the diagnostic accuracy of SSTR PET compared with 111 In-pentetreotide, 18 The inclusion and exclusion criteria for papers for this review were based on the study parameters established by the workgroup, using the PICOTS (population, intervention, comparisons, outcomes, timing, and setting) approach.…”