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Cost-Effectiveness Analysis of ⁶⁸Ga DOTA-TATE PET/CT, ¹¹¹In-Pentetreotide SPECT/CT and CT for Diagnostic Workup of Neuroendocrine Tumors.

ABSTRACT: Neuroendocrine tumors (NETs) are relatively rare neoplasms arising from the hormone-producing neuroendocrine system that can occur in various organs such as pancreas, small bowel, stomach and lung. As the majority of these tumors express somatostatin receptors (SSR) on their cell membrane, utilization of SSR analogs in nuclear medicine is a promising, but relatively costly approach for detection and localization. The aim of this study was to analyze the cost-effectiveness of ⁶⁸Ga-DOTA-TATE PET/CT (Gallium-68 DOTA-TATE Positron emission tomography/computed tomography) compared to ¹¹¹In-pentetreotide SPECT/CT (Indium-111 pentetreotide Single Photon emission computed tomography/computed tomography) and to CT (computed tomography) alone in detection of NETs. A decision model on the basis of Markov simulations evaluated lifetime costs and quality-adjusted life years (QALYs) related to either a CT, SPECT/CT or PET/CT. Model input parameters were obtained from publicized research projects. The analysis is grounded on the US healthcare system. Deterministic sensitivity analysis of diagnostic parameters and probabilistic sensitivity analysis predicated on a Monte Carlo simulation with 30,000 reiterations was executed. The willingness-to-pay (WTP) was determined to be $ 100,000/QALY. In the base-case investigation, PET/CT ended up with total costs of $88,003.07 with an efficacy of 4.179, whereas CT ended up with total costs of $88,894.71 with an efficacy of 4.165. SPECT/CT ended up with total costs of $89,973.34 with an efficacy of 4.158. Therefore, the strategies CT and SPECT/CT were dominated by PET/CT in the base-case scenario. In the sensitivity analyses, PET/CT remained a cost-effective strategy. This result was due to reduced therapy costs of timely detection. The additional costs of ⁶⁸Ga-DOTA-TATE PET/CT when compared to CT alone are justified in the light of potential savings in therapy costs and better outcomes.

SUBMITTER: Froelich MF

PROVIDER: S-EPMC7922846 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Cost-Effectiveness Analysis of 68Ga DOTA-TATE PET/CT, 111In-Pentetreotide SPECT/CT and CT for Diagnostic Workup of Neuroendocrine Tumors.

Froelich Matthias Frank MF Schnitzer Moritz Ludwig ML Holzgreve Adrien A Gassert Felix Gerhard FG Gresser Eva E Overhoff Daniel D Schwarze Vincent V Fabritius Matthias Philipp MP Nörenberg Dominik D von Münchhausen Niklas N Hokamp Nils Große NG Auernhammer Christoph J CJ Ilhan Harun H Todica Andrei A Rübenthaler Johannes J

Diagnostics (Basel, Switzerland) 20210218 2

Neuroendocrine tumors (NETs) are relatively rare neoplasms arising from the hormone-producing neuroendocrine system that can occur in various organs such as pancreas, small bowel, stomach and lung. As the majority of these tumors express somatostatin receptors (SSR) on their cell membrane, utilization of SSR analogs in nuclear medicine is a promising, but relatively costly approach for detection and localization. The aim of this study was to analyze the cost-effectiveness of 68Ga-DOTA ...[more]

PMID: 33670457

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Project description:PurposeIn the characterization of severe lung diseases, early detection of specific inflammatory cells could help to monitor patients' response to therapy and increase chances of survival. Macrophages contribute to regulating the resolution and termination of inflammation and have increasingly been of interest for targeted therapies. [68Ga]Ga-DOTA-TATE is an established clinical radiopharmaceutical targeting somatostatin receptor subtype 2 (SSTR 2). Since activated macrophages (M1) overexpress SSTR 2, the aim of this study was to investigate the applicability of [68Ga]Ga-DOTA-TATE for positron emission tomography (PET) imaging of M1 macrophages in pulmonary inflammation.MethodsInflammation in the pig lungs was induced by warm saline lavage followed by injurious ventilation in farm pigs (n = 7). Healthy pigs (n = 3) were used as control. A 60-min dynamic PET scan over the lungs was performed after [68Ga]Ga-DOTA-TATE injection and [18F]FDG scan was executed afterward for comparison. The uptake of both tracers was assessed as mean standardized uptake values (SUVmean) 30-60-min post-injection. The PET scans were followed by computed tomography (CT) scans, and the Hounsfield units (HU) were quantified of the coronal segments. Basal and apical segments of the lungs were harvested for histology staining. A rat lung inflammation model was also studied for tracer specificity using lipopolysaccharides (LPS) by oropharyngeal aspiration. Organ biodistribution, ex vivo autoradiography (ARG) and histology samples were conducted on LPS treated, octreotide induced blocking and control healthy rats.ResultsThe accumulation of [68Ga]Ga-DOTA-TATE on pig lavage model was prominent in the more severely injured dorsal segments of the lungs (SUVmean = 0.91 ± 0.56), compared with control animals (SUVmean = 0.27 ± 0.16, p < 0.05). The tracer uptake corresponded to the damaged areas assessed by CT and histology and were in line with HU quantification. The [68Ga]Ga-DOTA-TATE uptake in LPS treated rat lungs could be blocked and was significantly higher compared with control group.ConclusionThe feasibility of the noninvasive assessment of tissue macrophages using [68Ga]Ga-DOTA-TATE/PET was demonstrated in both porcine and rat lung inflammation models. [68Ga]Ga-DOTA-TATE has a great potential to be used to study the role and presence of macrophages in humans in fight against severe lung diseases.

Project description:BACKGROUND:Lanreotide is a long-acting somatostatin analogue with proven antitumour effects against well-differentiated (WD) gastroenteropancreatic-neuroendocrine tumours (GEP-NETs). However, there are no globally established prognostic factors associated with the efficacy of lanreotide as a treatment for GEP-NETs. We investigated the prognostic value of [68Ga]Ga-DOTA-TOC positron emission tomography (PET)/computed tomography (CT) somatostatin receptor imaging for patients with WD GEP-NETs treated with lanreotide. METHODS:In this retrospective study, we included 31 patients with unresectable or metastatic WD GEP-NETs who received lanreotide and underwent [68Ga]Ga-DOTA-TOC PET/CT before receiving lanreotide. We captured the following clinicopathological variables: Eastern Cooperative Oncology Group (ECOG) performance status, primary tumour site, NET World Health Organization grade, existence of carcinoid symptoms, previous surgery, previous chemotherapy, and hepatic tumour volume assessed by CT or magnetic resonance imaging (MRI). We also assessed the following [68Ga]Ga-DOTA-TOC PET/CT variables: Krenning score, tumour-to-liver ratio (TLR), maximum standardized uptake value (SUVmax), whole tumour volume (WTV), and total receptor expression (TRE, WTV multiplied by SUVmean). The associations between these markers and progression-free survival (PFS) with lanreotide were analysed. RESULTS:The mean age was 55.1 ± 15.5?years (range 16.0-81.0). The most common primary tumour site was the pancreas, followed by the stomach, and rectum. The median PFS interval with lanreotide was 14.4?months (range 1.3-34.9), with identified disease progression in 20 patients (64.5%). Among the [68Ga]Ga-DOTA-TOC PET/CT variables, TLR (< 8.1 vs. ? 8.1; p = 0.013), SUVmax (< 42.9 vs. ? 42.9; p = 0.037), and WTV (? 58.9?cm3 vs. < 58.9?cm3; p = 0.030) were significantly associated with PFS in the univariate analyses, but only TLR (hazard ratio 3.182 [95% CI 1.189-8.514], p = 0.021) remained an independent factor for PFS in the multivariate analysis. CONCLUSIONS:Low TLR, determined via [68Ga]Ga-DOTA-TOC PET/CT, can be a factor of worse prognosis in patients with advanced WD GEP-NETs treated with lanreotide.

Project description:A well-established approach for diagnostic imaging of osteomyelitis (OM), a bone infection, is simultaneous SPECT-CT of 99mTc sulfur colloid (SC) and 111In white blood cells (WBC). This method provides essentially perfect spatial registration of the tracers within anatomic sites of interest. Currently, diagnosis is based purely on a visual assessment-where relative discordance between 99mTc and 111In uptake in bone, i.e., high 111In and low 99mTc, suggests OM. To achieve more quantitative images, noise, scatter, and crosstalk between radionuclides must be addressed through reconstruction. Here the authors compare their Monte Carlo-based joint OSEM (MC-JOSEM) algorithm, which reconstructs both radionuclides simultaneously, to a more conventional triple-energy window-based reconstruction (TEW-OSEM), and to iterative reconstruction with no compensation for scatter (NC-OSEM).The authors created numerical phantoms of the foot and torso. Multiple bone-infection sites were modeled using high-count Monte Carlo simulation. Counts per voxel were then scaled to values appropriate for 111In WBC and 99mTc SC imaging. Ten independent noisy projection image sets were generated by drawing random Poisson deviates from these very low-noise images. Data were reconstructed using the two iterative scatter-compensation methods, TEW-OSEM and MC-JOSEM, as well as the uncorrected method (NC-OSEM). Mean counts in volumes of interest (VOIs) were used to evaluate the bias and precision of each method. Data were also acquired using a phantom, approximately the size of an adult ankle, consisting of regions representing infected and normal bone marrow, within a bone-like attenuator and surrounding soft tissue; each compartment contained a mixture of 111In and 99mTc. Low-noise data were acquired during multiple short scans over 29 h on a Siemens Symbia T6 SPECT-CT with medium-energy collimators. Pure 99mTc and 111In projection datasets were derived by fitting the acquired projections to the sum of 99mTc and 111In contributions, using the known half-lives. Uncontaminated data were scaled and recombined into six datasets with different activity ratios; ten Poisson noise realizations were then generated for each ratio. VOIs in each of the compartments were used to evaluate the bias and precision of each method with respect to reconstructions of uncontaminated datasets. In addition to the simulated and acquired phantom images, the authors reconstructed patient images with MC-JOSEM and TEW-OSEM. Patient reconstructions were assessed qualitatively for lesion contrast, spatial definition, and scatter.For all simulated and acquired infection phantoms, the root-mean squared-error of measured 99mTc activity was significantly improved with MC-JOSEM and TEW-OSEM in comparison to NC-OSEM reconstructions. While MC-JOSEM trended toward outperforming TEW-OSEM, the improvement was only found to be significant (p<0.001) for the acquired bone phantom in which a wide range of 111In∕99mTc concentration ratios were tested. In all cases, scatter correction did not significantly improve 111In quantitation.Compensation for scatter and crosstalk is useful for improving quality, bias, and precision of 99mTc activity estimates in simultaneous dual-radionuclide imaging of OM. The use of the more rigorous MC-based estimates provided marginal improvements over TEW. While the phantom results were encouraging, more subjects are needed to evaluate the usefulness of quantitative 111In∕99mTc SPECT-CT in the clinic.

Dataset Information

Cost-Effectiveness Analysis of ⁶⁸Ga DOTA-TATE PET/CT, ¹¹¹In-Pentetreotide SPECT/CT and CT for Diagnostic Workup of Neuroendocrine Tumors.

Publications

Cost-Effectiveness Analysis of <sup>68</sup>Ga DOTA-TATE PET/CT, <sup>111</sup>In-Pentetreotide SPECT/CT and CT for Diagnostic Workup of Neuroendocrine Tumors.

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