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Objective Pancreatic cancer is portrayed to become the second leading cause of cancer-related death within the next years. Potentially complicating surgical resection emphasizes the importance of an accurate TNM classification. In particular, the failure to detect features for non-resectability has profound consequences on patient outcomes and economic costs due to incorrect indication for resection. In the detection of liver metastases, contrast-enhanced MRI showed high sensitivity and specificity; however, the cost-effectiveness compared to the standard of care imaging remains unclear. The aim of this study was to analyze whether additional MRI of the liver is a cost-effective approach compared to routinely acquired contrast-enhanced computed tomography (CE-CT) in the initial staging of pancreatic cancer. Methods A decision model based on Markov simulation was developed to estimate the quality-adjusted life-years (QALYs) and lifetime costs of the diagnostic modalities. Model input parameters were assessed based on evidence from recent literature. The willingness-to-pay (WTP) was set to $100,000/QALY. To evaluate model uncertainty, deterministic and probabilistic sensitivity analyses were performed. Results In the base-case analysis, the model yielded a total cost of $185,597 and an effectiveness of 2.347 QALYs for CE-MR/CT and $187,601 and 2.337 QALYs for CE-CT respectively. With a net monetary benefit (NMB) of $49,133, CE-MR/CT is shown to be dominant over CE-CT with a NMB of $46,117. Deterministic and probabilistic survival analysis showed model robustness for varying input parameters. Conclusion Based on our results, combined CE-MR/CT can be regarded as a cost-effective imaging strategy for the staging of pancreatic cancer. Key Points • Additional MRI of the liver for initial staging of pancreatic cancer results in lower total costs and higher effectiveness. • The economic model showed high robustness for varying input parameters.

PurposeRectal cancer is one of the most frequent causes of cancer-related morbidity and mortality in the world. Correct identification of the TNM state in primary staging of rectal cancer has critical implications on patient management. Initial evaluations revealed a high sensitivity and specificity for whole-body PET/MRI in the detection of metastases allowing for metastasis-directed therapy regimens. Nevertheless, its cost-effectiveness compared with that of standard-of-care imaging (SCI) using pelvic MRI + chest and abdominopelvic CT is yet to be investigated. Therefore, the aim of this study was to analyze the cost-effectiveness of whole-body 18F FDG PET/MRI as an alternative imaging method to standard diagnostic workup for initial staging of rectal cancer.MethodsFor estimation of quality-adjusted life years (QALYs) and lifetime costs of diagnostic modalities, a decision model including whole-body 18F FDG PET/MRI with a hepatocyte-specific contrast agent and pelvic MRI + chest and abdominopelvic CT was created based on Markov simulations. For obtaining model input parameters, review of recent literature was performed. Willingness to pay (WTP) was set to $100,000/QALY. Deterministic sensitivity analysis of diagnostic parameters and costs was applied, and probabilistic sensitivity was determined using Monte Carlo modeling.ResultsIn the base-case scenario, the strategy whole-body 18F FDG PET/MRI resulted in total costs of $52,186 whereas total costs of SCI were at $51,672. Whole-body 18F FDG PET/MRI resulted in an expected effectiveness of 3.542 QALYs versus 3.535 QALYs for SCI. This resulted in an incremental cost-effectiveness ratio of $70,291 per QALY for PET/MRI. Thus, from an economic point of view, whole-body 18F FDG PET/MRI was identified as an adequate diagnostic alternative to SCI with high robustness of results to variation of input parameters.ConclusionBased on the results of the analysis, use of whole-body 18F FDG PET/MRI was identified as a feasible diagnostic strategy for initial staging of rectal cancer from a cost-effectiveness perspective.

Recent immunotherapeutic approaches have evolved as powerful treatment options with high anti-tumour responses involving the patient’s own immune system. Passive immunotherapy applies agents that enhance existing anti-tumour responses, such as antibodies against immune checkpoints. Active immunotherapy uses agents that direct the immune system to attack tumour cells by targeting tumour antigens. Active cellular-based therapies are on the rise, most notably chimeric antigen receptor T cell therapy, which redirects patient-derived T cells against tumour antigens. Approved treatments are available for a variety of solid malignancies including melanoma, lung cancer and haematologic diseases. These novel immune-related therapeutic approaches can be accompanied by new patterns of response and progression and immune-related side-effects that challenge established imaging-based response assessment criteria, such as Response Evaluation Criteria in Solid tumours (RECIST) 1.1. Hence, new criteria have been developed. Beyond morphological information of computed tomography (CT) and magnetic resonance imaging, positron emission tomography (PET) emerges as a comprehensive imaging modality by assessing (patho-)physiological processes such as glucose metabolism, which enables more comprehensive response assessment in oncological patients. We review the current concepts of response assessment to immunotherapy with particular emphasis on hybrid imaging with 18 F-FDG-PET/CT and aims at describing future trends of immunotherapy and additional aspects of molecular imaging within the field of immunotherapy.

PurposeRadiolabelled somatostatin analogues targeting somatostatin receptors (SSR) are well established for combined positron emission tomography/computer tomography (PET/CT) imaging of neuroendocrine tumours (NET). [18F]SiTATE has recently been introduced showing high image quality, promising clinical performance and improved logistics compared to the clinical reference standard 68Ga-DOTA-TOC. Here we present the first dosimetry and optimal scan time analysis.MethodsEight NET patients received a [18F]SiTATE-PET/CT (250 ± 66 MBq) with repeated emission scans (10, 30, 60, 120, 180 min after injection). Biodistribution in normal organs and SSR-positive tumour uptake were assessed. Dosimetry estimates for risk organs were determined using a combined linear-monoexponential model, and by applying 18F S-values and reference target masses for the ICRP89 adult male or female (OLINDA 2.0). Tumour-to-background ratios were compared quantitatively and visually between different scan times.ResultsAfter 1 h, normal organs showed similar tracer uptake with only negligible changes until 3 h post-injection. In contrast, tracer uptake by tumours increased progressively for almost all types of metastases, thus increasing tumour-to-background ratios over time. Dosimetry resulted in a total effective dose of 0.015 ± 0.004 mSv/MBq. Visual evaluation revealed no clinically relevant discrepancies between later scan times, but image quality was rated highest in 60 and 120 min images.Conclusion[18F]SiTATE-PET/CT in NET shows overall high tumour-to-background ratios from 60 to 180 min after injection and an effective dose comparable to 68Ga-labelled alternatives. For clinical use of [18F]SiTATE, the best compromise between image quality and tumour-to-background contrast is reached at 120 min, followed by 60 min after injection.

PurposeConventional ultrasound is the main imaging modality in obstetrics for assessing the maternal and fetal status. Up to date, contrast-enhanced ultrasound (CEUS) has not found widespread use in gynecology and obstetrics, but recent studies demonstrate promising results. The aim of the present study is to assess safe and valuable application of CEUS during pregnancy to investigate non-obstetric conditions.MethodsFive pregnant patients on whom CEUS was performed between 2019 and 2020 were included in this retrospective single-center study. A total of six CEUS examinations were performed including one CEUS-guided biopsy (mean age: 31 years, mean weeks of pregnancy: 18 weeks). CEUS examinations were performed by a consultant radiologist (EFSUMB level 3).ResultsAll included pregnant women safely underwent CEUS. Neither maternal nor fetal adverse effects were detected. CEUS critically helped in the diagnostic workup of a desmoid tumor of the abdominal wall, hepatic hemangioma, amebic hepatic abscess, uncomplicated renal cyst and post-inflammatory alteration of the renal cortex and for excluding active abdominal bleeding. In addition, CEUS-guided biopsy was performed to prevent intratumoral hemorrhage. Findings from CEUS prompted immediate treatment in two women, whereas in three women regular obstetric monitoring of the women could be conducted.ConclusionOur results demonstrate safe and crucial application of off-label CEUS in pregnant women to assess different non-obstetric conditions allowing to prevent additional ionizing CT or application of (gadolinium-based) contrast agent in MRI. Hence, CEUS might add pivotal value for evaluating obstetric and non-obstetric conditions and thereby directing clinical management of pregnant women in the future.

Objective Hepatocellular carcinoma (HCC) is the most common cause of primary liver cancer. A major part of diagnostic HCC work-up is based on imaging findings from sonography, computed tomography (CT), or magnetic resonance imaging (MRI) scans. Contrast-enhanced ultrasound (CEUS) allows for the dynamic assessment of the microperfusion pattern of suspicious liver lesions. This study aimed to evaluate the diagnostic value of CEUS compared with CT scans for assessing HCC. Methods We performed a retrospective, single-center study between 2004 and 2018 on 234 patients with suspicious liver lesions who underwent CEUS and CT examinations. All patients underwent native B-mode, color Doppler and CEUS after providing informed consent. Every CEUS examination was performed and interpreted by a single experienced radiologist (European Federation of Societies for Ultrasound in Medicine and Biology level 3). Results CEUS was performed on all included patients without occurrence of any adverse effects. CEUS showed a sensitivity of 94%, a specificity of 70%, a positive predictive value of 93% and a negative predictive value of 72% for analyzing HCC compared with CT as the diagnostic gold standard. Conclusions CEUS has an excellent safety profile and shows a high diagnostic accuracy in assessing HCC compared with corresponding results from CT scans.

Our retrospective single-center study aims to evaluate the impact of structured reporting (SR) using a self-developed template on report quality compared to free-text reporting (FTR) in [ 18 F]SiTATE Positron Emission Tomography/Computer Tomography (PET/CT) for the primary staging and therapy monitoring of patients diagnosed with neuroendocrine tumors (NET). In total 50 patients were included. FTRs and SRs were generated post-examination. All reports were evaluated by a radiologist and a surgeon through a questionnaire to determine their contribution to facilitating clinical decision-making and to assess their completeness, linguistic quality, and overall quality. SR significantly increased the capacity of facilitating therapy decision-making from 32% in FTR to 55% in SR ( p  < 0.001). Trust in the report was significantly higher in SR with a mean of 5.0 (SD = 0.5) vs. 4.7 (SD = 0.5) for FTR ( p  < 0.001). SR received significantly higher mean ratings regarding linguistic quality with 4.7 for SR vs. 4.4 for FTR ( p  = 0.004) and overall report quality with a mean of 4.9 for SR vs. 4.6 for FTR ( p  < 0.001). Concluding that SR enhances the overall quality of reports in [ 18 F]SiTATE-PET/CTs for NET staging, serving as a tool to streamline clinical decision-making and enhance interdisciplinary communication in the future.

Background: Colorectal cancer is among the most prevalent cancer entities worldwide, with every second patient developing liver metastases during their illness. For local treatment of liver metastases, a surgical approach as well as ablative treatment options, such as microwave ablation (MWA) and radiofrequency ablation (RFA), are available. The aim of this study is to evaluate the cost-effectiveness of RFA, MWA and surgery in the treatment of liver metastases of oligometastatic colorectal cancer (omCRC) that are amenable for all investigated treatment modalities. Methods: A decision analysis based on a Markov model assessed lifetime costs and quality-adjusted life years (QALY) related to the treatment strategies RFA, MWA and surgical resection. Input parameters were based on the best available and most recent evidence. Probabilistic sensitivity analyses (PSA) were performed with Monte Carlo simulations to evaluate model robustness. The percentage of cost-effective iterations was determined for different willingness-to-pay (WTP) thresholds. Results: The base-case analysis showed that surgery led to higher long-term costs compared to RFA and MWA (USD 41,848 vs. USD 36,937 vs. USD 35,234), while providing better long-term outcomes than RFA, yet slightly lower than MWA (6.80 vs. 6.30 vs. 6.95 QALYs for surgery, RFA and MWA, respectively). In PSA, MWA was the most cost-effective strategy for all WTP thresholds below USD 80,000 per QALY. Conclusions: In omCRC patients with liver metastases, MWA and surgery are estimated to provide comparable efficacy. MWA was identified as the most cost-effective strategy in intermediate resource settings and should be considered as an alternative to surgery in high resource settings.

Background: To evaluate the diagnostic accuracy of quantitative perfusion parameters in contrast-enhanced ultrasound to differentiate malignant from benign liver lesions. Methods: In this retrospective study 134 patients with a total of 139 focal liver lesions were included who underwent contrast enhanced ultrasound (CEUS) between 2008 and 2018. All examinations were performed by a single radiologist with more than 15 years of experience using a second-generation blood pool contrast agent. The standard of reference was histopathology (n = 60), MRI or CT (n = 75) or long-term CEUS follow up (n = 4). For post processing regions of interests were drawn both inside of target lesions and the liver background. Time–intensity curves were fitted to the CEUS DICOM dataset and the rise time (RT) of contrast enhancement until peak enhancement, and a late-phase ratio (LPR) of signal intensities within the lesion and the background tissue, were calculated and compared between malignant and benign liver lesion using Student’s t-test. Quantitative parameters were evaluated with respect to their diagnostic accuracy using receiver operator characteristic curves. Both features were then combined in a logistic regression model and the cumulated accuracy was assessed. Results: RT of benign lesions (14.8 ± 13.8 s, p = 0.005), and in a subgroup analysis, particular hemangiomas (23.4 ± 16.2 s, p < 0.001) differed significantly to malignant lesions (9.3 ± 3.8 s). The LPR was significantly different between benign (1.59 ± 1.59, p < 0.001) and malignant lesions (0.38 ± 0.23). Logistic regression analysis with RT and LPR combined showed a high diagnostic accuracy of quantitative CEUS parameters with areas under the curve of 0.923 (benign vs. malignant) and 0.929 (hemangioma vs. malignant. Conclusions: Quantified CEUS parameters are helpful to differentiate malignant from benign liver lesions, in particular in case of atypical hemangiomas.

Background/Objectives: Peptide Receptor Radionuclide Therapy (PRRT) is approved for patients with inoperable, progressive and/or metastatic well-differentiated NETs. Before the approval of Lutathera®, locally manufactured 177Lu-HA-DOTATATE was used on a regular basis in clinical routine. The aim of this study was (1) to compare the hematotoxicity of locally manufactured 177Lu-HA-DOTATATE with Lutathera® in GEP-NET patients and (2) to compare the recommended treatment interval of 8 weeks between each cycle to a prolonged scheme of up to 11 weeks for both 177Lu-HA-DOTATATE and Lutathera®. Methods: The included patients with GEP NETs (n = 46) received four cycles of PRRT, either 177Lu-HA-DOTATATE or Lutathera®, and were divided into four subgroups. The subgroups were treated with either locally manufactured 177Lu-HA-DOTATATE or Lutathera® and were stratified into a mean application interval of 8 (HA8weeks, n = 10/Lutathera8weeks, n = 16) or 11 weeks (HAadapted, n = 10/Lutatheraadapted, n = 10). To evaluate therapy associated hemato- and nephrotoxicity, patients underwent two laboratory follow-up examinations (follow-up 1—between 2./3. therapy cycle; follow-up 2—after the termination of the 4. therapy cycle) and were then compared to pre-PRRT laboratory results. To assess hematological and renal recovery trends, blood values and parameters of kidney function were collected up to 58.9 weeks after PRRT completion. Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) were used for grading hematological parameters. Results: The occurrence of high-grade adverse events (CTCAE grade 3/4) after PRRT was moderate, with 1/10 (10%) grade 4 lymphocytopenia in the Lutatheraadapted group, while overall, 20/46 (43.5%) patients had grade 3 lymphocytopenia. Grade 3 thrombocytopenia occurred in 1/10 (10%) patients of the HAadapted group. Absolute and percentage changes in the kidney function (creatinine, TER) remained constant during PRRT in all subgroups. All four subgroups showed a significant decrease in absolute blood value changes for PLT counts, WBC counts, neutrophil granulocytes and lymphocytes between, prior to and after PRRT (p < 0.05, each). Regarding percentage changes in laboratory parameters, only the HAadapted and the HA8weeks groups had significant decreases in WBC (p < 0.03, each) and PLT counts (p < 0.04, each) while there was no significant degradation of any other hematological parameter in any of the subgroups. Only patients with longer treatment intervals under 177Lu-HA-DOTATATE therapy showed a statistically significant correlation in the long-term recovery analysis concerning the PLT counts (r = 0.6, p < 0.0001). Other blood and kidney values showed no significant correlation in the long-term analysis in the other subgroups. Conclusion: Comparing the hematotoxicity in patients that were treated with locally manufactured 177Lu-HA-DOTATATE with patients that were treated with Lutathera® and assessing different treatment intervals in both groups (8 vs. 11 weeks), revealed that there is overall a low to moderate incidence of significant changes in hematological and renal parameters directly after PRRT. Recovery trends of hematological and renal parameters after 1 year suggest that patients treated with locally manufactured 177Lu-HA-DOTATATE might benefit from a longer treatment interval of 11 weeks regarding their PLT counts. Given the risk of developing hematological diseases such as therapy-related myeloid neoplasms years after PRRT, longer observational periods after PRRT will be crucial.