Systematic literature reviews (SLRs) are fundamental for aggregating published evidence, identifying knowledge gaps and informing health economic evaluations, especially in the field of novel diagnostics where randomised controlled trials are commonly absent [1]. The global publishing output within the field of novel diagnostics is increasing rapidly owing to increasing efforts towards precision medicine. Simultaneously, the global publishing output within the field of health economics is increasing rapidly owing to increasing efforts towards value-based healthcare and present budget constraints. The number of publications focussing on the health economic impact of diagnostics almost doubled from 86,244 in 2010 to 152,404 in 2025 (PubMed search using MeSH terms ‘Diagnostic Techniques and Procedures’ and ‘Health Care Economics and Organizations’). Consequently, the workload of performing SLRs is increasing as the number of articles that requires screening grows larger. The average time to complete an SLR is over 15 months, while the proportion of truly relevant articles for data extraction may be as low as 1% of the total search results [2]. The high workload may reduce researchers’ willingness to conduct an SLR or may lead to search strategies that are too narrow when prioritising time constraints over review quality. Moreover, it may render an SLR outdated by the time it is published.

Background: Prior studies show that short-term treatment using tyrosine kinase inhibitors (TKIs) can reinduce radioiodine uptake and warrant ¹³¹I therapy in radioiodine-refractory differentiated thyroid cancer (RAI-R DTC). We aim to evaluate the potential of standard-of-care TKI lenvatinib to reinduce clinically meaningful radioiodine retention. Methods: Nine RAI-R DTC patients starting lenvatinib treatment for progressive advanced or metastatic disease, were included and underwent rhTSH-stimulated ¹²⁴I dosimetric procedures at baseline, week 6 (N=7) and week 12 (N=8). At all timepoints, the fraction of patients eligible for ¹³¹I therapy with a maximal activity of 7.4 GBq was assessed. Patients were considered eligible if at least one target lesion showed an expected mean absorbed dose ≥20 Gy. In total, 23 target lesions were segmented on¹²⁴I PET/CT images and their volumes estimated using low-dose CT images. Lesion size-specific recovery correction was applied to the measured mean activity concentration at each timepoint. Tumor dosimetry was performed using a mono-exponential fit and S-values from an internal dosimetry program for diagnostic nuclear medicine based on the ICRP adult reference voxel phantoms (IDAC-Dose2.1). Mean absorbed lesion dose per administered activity (LDpA), 24h-uptake and residence time in target lesions were compared between time points. Results: By our definition, none of the patients were found eligible for ¹³¹I therapy at any timepoint. Lenvatinib-induced partial response was observed in 59% and 75% of target lesions at week 6 and 12, respectively. Median LDpA was 0.08 (IQR: 0.04-0.17), 0.18 (0.08-0.36) and 0.17 (0.09-0.37) Gy/GBq for week 0, 6 and 12, respectively (p=0.08). The 24h-uptake and residence time were comparable between timepoints (p>0.22). Conclusion: Redifferentiation of RAI-R DTC to reinduce radioiodine uptake to a level that warrants ¹³¹I therapy may not be established by short-term lenvatinib treatment. Multi-targeted TKIs may not be as potent as selective TKIs in reinducing clinically meaningful radioiodine retention.

Background and Objective
This systematic literature review addresses model-based cost-effectiveness studies for therapy response monitoring with positron emission tomography (PET) generally combined with low-dose computed tomography (CT) for various cancer types. Given the known heterogeneity in therapy response events, studies should consider patient-level modelling rather than cohort-based modelling because of its flexibility in handling these events and the time to events. This review aims to identify the modelling methods used and includes a systematic assessment of the assumptions made in the current literature.

Methods
This study was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. Information sources included electronic bibliographic databases, reference lists of review articles and contact with experts in the fields of nuclear medicine, health technology assessment and health economics. Eligibility criteria included peer-reviewed scientific publications and published grey literature. Literature searches, screening and critical appraisal were conducted by two reviewers independently. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) were used to assess the methodological quality. The Bias in Economic Evaluation (ECOBIAS) checklist was used to determine the risk of bias in the included publications.

Results
The search results included 2959 publications. The number of publications included for data extraction and synthesis was ten, representing eight unique studies. These studies addressed patients with lymphoma, advanced head and neck cancers, brain tumours, non-small cell lung cancer and cervical cancer. All studies addressed response to chemotherapy. No study evaluated response to immunotherapy. Most studies positioned PET/CT as an add-on modality and one study positioned PET/CT as a replacement for conventional imaging (X-ray and contrast-enhanced CT). Three studies reported decision-tree structures, four studies reported cohort-level state-transition models and one study reported a partitioned survival model. No patient-level models were reported. The simulation horizons adopted ranged from 1 year to lifetime. Most studies reported a probabilistic analysis, whereas two studies reported a deterministic analysis only. Two studies conducted a value of information analysis. Multiple studies did not adequately discuss model-specific aspects of bias. Most importantly and regularly observed were a high risk of structural assumptions bias, limited simulation horizon bias and wrong model bias.

Conclusions
Model-based cost-effectiveness analysis for therapy response monitoring with PET/CT was based on cohorts of patients instead of individual patients in the current literature. Therefore, the heterogeneity in therapy response events was commonly not addressed appropriately. Further research should include more advanced and patient-level modelling approaches to accurately represent the complex context of clinical practice and, therefore, to be meaningful to support decision making.

Registration
This review is registered in PROSPERO, the international prospective register of systematic reviews funded by the National Institute for Health Research, with CRD42023402581.

Purpose: We conducted a cost-effectiveness analysis in which we compared a preoperative [¹⁸F]Fluorocholine PET/CT-based one-stop-shop imaging strategy with current best practice in which [¹⁸F]Fluorocholine PET/CT is only recommended after negative or inconclusive [^99mTc]Tc-methoxy isobutyl isonitrile SPECT/CT for patients suffering from primary hyperparathyroidism. We investigated whether the one-stop-shop strategy performs as well as current best practice but at lower costs. Methods: We developed a cohort-level state transition model to evaluate both imaging strategies respecting an intraoperative parathyroid hormone monitored treatment setting as well as a traditional treatment setting. The model reflects patients’ hospital journeys after biochemically diagnosed primary hyperparathyroidism. A cycle length of twelve months and a lifetime horizon were used. We conducted probabilistic analyses simulating 50,000 cohorts to assess joint parameter uncertainty. The incremental net monetary benefit and cost for each quality-adjusted life year were estimated. Furthermore, threshold analyses regarding the tariff of [¹⁸F]Fluorocholine PET/CT and the sensitivity of [^99mTc]Tc-methoxy isobutyl isonitrile SPECT/CT were performed. Results: The simulated long-term health effects and costs were similar for both imaging strategies. Accordingly, there was no incremental net monetary benefit and the one-stop-shop strategy did not result in lower costs. These results applied to both treatment settings. The threshold analysis indicated that a tariff of €885 for [¹⁸F]Fluorocholine PET/CT was required to be cost-effective compared to current best practice. Conclusion: Both preoperative imaging strategies can be used interchangeably. Daily clinical practice grounds such as available local resources and patient preferences should inform policy-making on whether a hospital should implement the one-stop-shop imaging strategy.

Background: Central necrosis can be detected on [¹⁸F]FDG PET/CT as a region with little to no tracer uptake. Currently, there is no consensus regarding the inclusion of regions of central necrosis during volume of interest (VOI) delineation for radiomic analysis. The aim of this study was to assess how central necrosis affects radiomic analysis in PET. Methods: Forty-three patients, either with non-small cell lung carcinomas (NSCLC, n = 12) or with pheochromocytomas or paragangliomas (PPGL, n = 31), were included retrospectively. VOIs were delineated with and without central necrosis. From all VOIs, 105 radiomic features were extracted. Differences in radiomic features between delineation methods were assessed using a paired t-test with Benjamini-Hochberg multiple testing correction. In the PPGL cohort, performances of the radiomic models to predict the noradrenergic biochemical profile were assessed by comparing the areas under the receiver operating characteristic curve (AUC) for both delineation methods. Results: At least 65% of the features showed significant differences between VOI_vital-tumour and VOI_gross-tumour (65%, 79% and 82% for the NSCLC, PPGL and combined cohort, respectively). The AUCs of the radiomic models were not significantly different between delineation methods. Conclusion: In both tumour types, almost two-third of the features were affected, demonstrating that the impact of whether or not to include central necrosis in the VOI on the radiomic feature values is significant. Nevertheless, predictive performances of both delineation methods were comparable. We recommend that radiomic studies should report whether or not central necrosis was included during delineation.