Diagnostic accuracy of SSR-PET/CT compared to histopathology in the identification of liver metastases from well-differentiated neuroendocrine tumors.

BACKGROUND: Histopathology is the reference standard for diagnosing liver metastases of neuroendocrine tumors (NETs). Somatostatin receptor-positron emission tomography / computed tomography (SSR-PET/CT) has emerged as a promising non-invasive imaging modality for staging NETs. We aimed to assess the diagnostic accuracy of SSR-PET/CT in the identification of liver metastases in patients with proven NETs compared to histopathology. METHODS: Histopathologic reports of 139 resected or biopsied liver lesions of patients with known NET were correlated with matching SSR-PET/CTs and the positive/negative predictive value (PPV/NPV), sensitivity, specificity, and diagnostic accuracy of SSR-PET/CT were evaluated. PET/CT reading was performed by one expert reader blinded to histopathology and clinical data. RESULTS: 133 of 139 (95.7%) liver lesions showed malignant SSR-uptake in PET/CT while initial histopathology reported on 'liver metastases of NET´ in 127 (91.4%) cases, giving a PPV of 91.0%. Re-biopsy of the initially histopathologically negative lesions (reference standard) nevertheless diagnosed 'liver metastases of NET' in 6 cases, improving the PPV of PET/CT to 95.5%. Reasons for initial false-negative histopathology were inadequate sampling in the sense of non-target biopsies. The 6 (4.3%) SSR-negative lesions were all G2 NETs with a Ki-67 between 2-15%. CONCLUSION: SSR-PET/CT is a highly accurate imaging modality for the diagnosis of liver metastases in patients with proven NETs. However, we found that due to the well-known tumor heterogeneity of NETs, specifically in G2 NETs approximately 4-5% are SSR-negative and may require additional imaging with [18F]FDG PET/CT.

Cancer of unknown primary (CUP) through the lens of precision oncology: a single institution perspective.

PURPOSE: For patients with cancer of unknown primary (CUP), treatment options are limited. Precision oncology, the interplay of comprehensive genomic profiling (CGP) and targeted therapies, aims to offer additional treatment options to patients with advanced and hard-to-treat cancers. We aimed to highlight the use of a molecular tumor board (MTB) in the therapeutic management of CUP patients. METHODS: In this single-center observational study, CUP patients, presented to the MTB of the Comprehensive Cancer Center Munich LMU, a tertiary care center, were analyzed retrospectively. Descriptive statistics were applied to describe relevant findings. RESULTS: Between June 2016 and February 2022, 61 patients with unfavorable CUP were presented to the MTB, detected clinically relevant variants in 74% (45/61) of patients, of which 64% (29/45) led to therapeutic recommendation. In four out of 29 patients (14%), the treatment recommendations were implemented, unfortunately without resulting in clinical benefit. Reasons for not following the therapeutic recommendation were mainly caused by the physicians' choice of another therapy (9/25, 36%), especially in the context of worsening of general condition, lost to follow-up (7/25, 28%) and death (6/25, 24%). CONCLUSION: CGP and subsequent presentation to a molecular tumor board led to a high rate of therapeutic recommendations in patients with CUP. Recommendations were only implemented at a low rate; however, late GCP diagnostic and, respectively, MTB referral were found more frequent for the patients with implemented treatment. This contrast underscores the need for early implementation of CGP into the management of CUP patients.

Diagnostic Performance of Whole-Body Ultra-Low-Dose CT for Detection of Mechanical Ventriculoperitoneal Shunt Complications: A Retrospective Analysis.

BACKGROUND AND PURPOSE: Radiographic shunt series are still the imaging technique of choice for radiologic evaluation of VP-shunt complications. Radiographic shunt series are associated with high radiation exposure and have a low diagnostic performance. Our aim was to investigate the diagnostic performance of whole-body ultra-low-dose CT for detecting mechanical ventriculoperitoneal shunt complications. MATERIALS AND METHODS: This retrospective study included 186 patients (mean age, 54.8 years) who underwent whole-body ultra-low-dose CT (100 kV[peak]; reference, 10 mAs). Two radiologists reviewed the images for the presence of ventriculoperitoneal shunt complications, image quality, and diagnostic confidence. On a 5-point Likert scale, readers scored image quality and diagnostic confidence (1 = very low, 5 = very high). Sensitivity, specificity, positive predictive value, and negative predictive value were calculated. Radiation dose estimation of whole-body ultra-low-dose CT was calculated and compared with the radiation dose of a radiographic shunt series. RESULTS: 34 patients positive for VP-shunt complications were correctly identified on whole-body ultra-low-dose CT by both readers. No false-positive or -negative cases were recorded by any of the readers, yielding a sensitivity of 100% (95% CI, 87.3%-100%), a specificity of 100% (95% CI, 96.9%-100%), and perfect agreement (κ = 1). Positive and negative predictive values were high at 100%. Shunt-specific image quality and diagnostic confidence were very high (median score, 5; range, 5-5). Interobserver agreement was substantial for image quality (κ = 0.73) and diagnostic confidence (κ = 0.78). The mean radiation dose of whole-body ultra-low-dose CT was significantly lower than the radiation dose of a conventional radiographic shunt series (0.67 [SD, 0.4] mSv versus 1.57 [SD, 0.6] mSv; 95% CI, 0.79-1.0 mSv; P < .001). CONCLUSIONS: Whole-body ultra-low-dose CT allows detection of ventriculoperitoneal shunt complications with excellent diagnostic accuracy and diagnostic confidence. With concomitant radiation dose reduction on contemporary CT scanners, whole-body ultra-low-dose CT should be considered an alternative to the radiographic shunt series.

Cost-effectiveness of stress CTP versus CTA in detecting obstructive CAD or in-stent restenosis in stented patients.

OBJECTIVES: The aim of this retrospective study was to determine cost-effectiveness of stress myocardial CT perfusion (CTP), coronary CT angiography (CTA), and the combination of both in suspected obstructive coronary artery disease (CAD) or in-stent restenosis (ISR) in patients with previous coronary stent implantation. METHODS: A decision model based on Markov simulations estimated lifetime costs and quality-adjusted life years (QALYs) associated with CTA, CTP, and CTA + CTP. Model input parameters were obtained from published literature. Probabilistic sensitivity analysis was performed to evaluate overall model uncertainty. A single-variable deterministic sensitivity analysis evaluated the sensitivity of the results to plausible variations in model inputs. Cost-effectiveness was assessed based on a cost-effectiveness threshold of $100,000 per QALY. RESULTS: In the base-case scenario with willingness to pay of $100,000 per QALY, CTA resulted in total costs of $47,013.87 and an expected effectiveness of 6.84 QALYs, whereas CTP resulted in total costs of $46,758.83 with 6.93 QALYs. CTA + CTP reached costs of $47,455.63 with 6.85 QALYs. Therefore, strategies CTA and CTA + CTP were dominated by CTP in the base-case scenario. Deterministic sensitivity analysis demonstrated robustness of the model to variations of diagnostic efficacy parameters and costs in a broad range. CTP was cost-effective in the majority of iterations in the probabilistic sensitivity analysis as compared with CTA. CONCLUSIONS: CTP is cost-effective for the detection of obstructive CAD or ISR in patients with previous stenting and therefore should be considered a feasible approach in daily clinical practice. KEY POINTS: • CTP provides added diagnostic value in patients with previous coronary stents. • CTP is a cost-effective method for the detection of obstructive CAD or ISR in patients with previous stenting.

18F-PSMA-1007 PET/CT for response assessment in patients with metastatic renal cell carcinoma undergoing tyrosine kinase or checkpoint inhibitor therapy: preliminary results.

INTRODUCTION: Tyrosine kinase (TKI) and checkpoint inhibitors (CI) prolonged overall survival in metastatic renal cell carcinoma (mRCC). Early prediction of treatment response is highly desirable for the individualization of patient management and improvement of therapeutic outcome; however, serum biochemistry is unable to predict therapeutic efficacy. Therefore, we compared 18F-PSMA-1007 PET imaging for response assessment in mRCC patients undergoing TKI or CI therapy compared to CT-based response assessment as the current imaging reference standard. METHODS: 18F-PSMA-1007 PET/CT was performed in mRCC patients prior to initiation of systemic treatment and 8 weeks after therapy initiation. Treatment response was evaluated separately on 18F-PSMA-PET and CT. Changes on PSMA-PET (SUVmean) were assessed on a per patient basis using a modified PERCIST scoring system. Complete response (CRPET) was defined as absence of any uptake in all target lesions on posttreatment PET. Partial response (PRPET) was defined as decrease in summed SUVmean of > 30%. The appearance of new, PET-positive lesions or an increase in summed SUVmean of > 30% was defined as progressive disease (PDPET). A change in summed SUVmean of ± 30% defined stable disease (SDPET). RECIST 1.1 criteria were used for response assessment on CT. Results of radiographic response assessment on PSMA-PET and CT were compared. RESULTS: Overall, 11 mRCC patients undergoing systemic treatment were included. At baseline PSMA-PET1, all mRCC patients showed at least one PSMA-avid lesion. On follow-up PET2, 3 patients showed CRPET, 3 PRPET, 4 SDPET, and 1 PDPET. According to RECIST 1.1, 1 patient showed PRCT, 9 SDCT, and 1 PDCT. Overall, concordant classifications were found in only 2 cases (2 SDCT + PET). Patients with CRPET on PET were classified as 3 SDCT on CT using RECIST 1.1. By contrast, the patient classified as PRCT on CT showed PSMA uptake without major changes during therapy (SDPET). However, among 9 patients with SDCT on CT, 3 were classified as CRPET, 3 as PRPET, 1 as PDPET, and only 2 as SDPET on PSMA-PET. CONCLUSION: On PSMA-PET, heterogeneous courses were observed during systemic treatment in mRCC patients with highly diverging results compared to RECIST 1.1. In the light of missing biomarkers for early response assessment, PSMA-PET might allow more precise response assessment to systemic treatment, especially in patients classified as SD on CT.

Recent advances of PET imaging in clinical radiation oncology.

Radiotherapy and radiation oncology play a key role in the clinical management of patients suffering from oncological diseases. In clinical routine, anatomic imaging such as contrast-enhanced CT and MRI are widely available and are usually used to improve the target volume delineation for subsequent radiotherapy. Moreover, these modalities are also used for treatment monitoring after radiotherapy. However, some diagnostic questions cannot be sufficiently addressed by the mere use standard morphological imaging. Therefore, positron emission tomography (PET) imaging gains increasing clinical significance in the management of oncological patients undergoing radiotherapy, as PET allows the visualization and quantification of tumoral features on a molecular level beyond the mere morphological extent shown by conventional imaging, such as tumor metabolism or receptor expression. The tumor metabolism or receptor expression information derived from PET can be used as tool for visualization of tumor extent, for assessing response during and after therapy, for prediction of patterns of failure and for definition of the volume in need of dose-escalation. This review focuses on recent and current advances of PET imaging within the field of clinical radiotherapy / radiation oncology in several oncological entities (neuro-oncology, head & neck cancer, lung cancer, gastrointestinal tumors and prostate cancer) with particular emphasis on radiotherapy planning, response assessment after radiotherapy and prognostication.

Addressing a real-life problem: treatment with intravenous thrombolysis and mechanical thrombectomy in acute stroke patients with an extended time window beyond 4.5 h based on computed tomography perfusion imaging.

BACKGROUND AND PURPOSE: Acute ischemic stroke treatment with intravenous thrombolysis (IVT) is restricted to a time window of 4.5 h after known or presumed onset. Recently, magnetic resonance imaging-guided treatment decision-making in wake-up stroke (WUS) was shown to be effective. The aim of this study was to determine the safety and outcome of IVT in patients with a time window beyond 4.5 h selected by computed tomography perfusion (CTP) imaging. METHODS: We analyzed all consecutive patients last seen well beyond 4.5 h after stroke onset treated with IVT based on CTP between January 2015 and October 2018. CTP was visually assessed to estimate the mismatch between cerebral blood flow and cerebral blood volume maps. Early infarct signs were documented according to Alberta Stroke Program Early CT Score (ASPECTS). Safety data were obtained for mortality and symptomatic intracerebral hemorrhage (sICH). Follow-up was assessed with the modified Rankin Scale (mRS). RESULTS: A total of 70 patients fulfilled the inclusion criteria (mean age ± SD 77.6 ± 11.5 years, 50.0% female). Median National Institutes of Health Stroke Scale score on admission was 8.0 [interquartile range (IQR), 4-14]. The most frequent reasons for an extended time window were WUS (60.0%) and delayed hospital admission (27.1%). Median time from last seen well to IVT was 11.4 h. Median ASPECTS was 10 (IQR, 9-10) and CTP mismatch 90% (IQR, 80%-100%). A total of 24 patients (34.3%) underwent additional mechanical thrombectomy. sICH occurred in four patients (5.7%). At follow-up, 49.3% had an mRS score of 0-2 and 22.4% had an mRS score of 0-1. CONCLUSIONS: In patients presenting in an extended time window beyond 4.5 h, IVT treatment with decision-making based on CTP might be a safe procedure. Further evaluation in clinical trials is needed.

Imaging Triage of Patients with Late-Window (6-24 Hours) Acute Ischemic Stroke: A Comparative Study Using Multiphase CT Angiography versus CT Perfusion.

BACKGROUND AND PURPOSE: The role of collateral imaging in selecting patients for endovascular thrombectomy beyond 6 hours from onset has not been established. To assess the comparative utility of collateral imaging using multiphase CTA in selecting late window patients for EVT. MATERIALS AND METHODS: We used data from a prospective multicenter observational study in which all patients underwent imaging with multiphase CT angiography as well as CTP. Two blinded reviewers evaluated patients' eligibility for endovascular thrombectomy using published collateral imaging (multiphase CTA) criteria compared with CTP using the selection criteria of the Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention with Trevo (DAWN) and Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE-3) trials. CTP images were processed using automated commercial software. The outcomes of patients eligible for endovascular thrombectomy according to multiphase CTA, DAWN, or DEFUSE-3 criteria were compared using multivariable logistic regression modeling. Model characteristics were compared using the C-statistic for the receiver operating characteristic curve, the Akaike information criterion, and the Bayesian information criterion. RESULTS: Eighty-six patients presented beyond 6 hours from onset/last known well (median, 9.6 hours; interquartile range, 4.1 hours). Thirty-five patients (40.7%) received endovascular thrombectomy, of whom good functional outcome (90-day mRS, 0-2) was achieved in 16/35 (47%). Collateral-based imaging paradigms significantly modified the treatment effect of endovascular thrombectomy on 90-day mRS 0-2 (P interaction = .007). The multiphase CTA-based regression model best fit the data for the 90-day outcome (C-statistic, 0.86; 95% CI, 0.77-0.94) and was associated with the least information loss (Akaike information criterion, 95.7; Bayesian information criterion, 114.9) compared with CTP-based models. CONCLUSIONS: The collateral-based imaging paradigm using multiphase CTA compares well with CTP in selecting patients for endovascular thrombectomy in the late time window.

[Pheochromocytoma and paraganglioma : Importance of diagnostic imaging]. / Phäochromozytom und Paragangliom : Stellenwert der bildgebenden Diagnostik.

CLINICAL BACKGROUND: If pheochromocytoma (PC) or paraganglioma (PGL) is diagnosed based on serologic studies, imaging is required to locate the adrenal mass for further management. Besides pathognomonic hormonal findings, PC/PGL can exhibit typical imaging features. However, PC/PGL can also show morphological overlap with other pathologies. STANDARD RADIOLOGICAL METHODS: The modality of choice for evaluation of PC is CT. In case of extra-adrenal location, MRI is superior to CT. Imaging with PET-CT provides complementary information in the differentiation of PC/PGL and is recommended as the imaging modality of choice for malignant PC/PGL. 68Ga-DOTATATE (or 68Ga-DOTATOC/ 68Ga-DOTANOC) PET-CT has high sensitivity for SDHx-mutated PC/PGL and serves for planning of radioreceptor therapy with somatostatin analogues. In contrast, 123I-metaiodobenzylguanidine (MIBG) scintigraphy is important in assessing the potential efficacy of radioreceptor therapy with MIBG. METHODICAL DETAILS: The CT protocol for PC evaluation should include non-enhanced, arterial, portal-venous and late phases; the latter for the evaluation of wash-out. Recent studies indicate non-enhanced CT alone may be sufficient to rule out PC. For MRI, in- and opposed-phase sequences should be additionally acquired. PRACTICAL RECOMMENDATIONS: A relevant proportion of PC is diagnosed incidentally. Therefore, imaging of PC will gain further importance. Recent studies show better response rates of PC/PGL after radioreceptor therapy with somatostatin analogues (177Lu-DOTATATE) than with MIBG. Therefore, 68Ga-DOTATATE PET-CT gains further importance-for diagnostic imaging and therapy planning.

Imaging of Patients with Suspected Large-Vessel Occlusion at Primary Stroke Centers: Available Modalities and a Suggested Approach.

The overwhelming benefit of endovascular therapy in patients with large-vessel occlusions suggests that more patients will be screened than treated. Some of those patients will be evaluated first at primary stroke centers; this type of evaluation calls for standardizing the imaging approach to minimize delays in assessing, transferring, and treating these patients. Here, we propose that CT angiography (performed at the same time as head CT) should be the minimum imaging approach for all patients with stroke with suspected large-vessel occlusion presenting to primary stroke centers. We discuss some of the implications of this approach and how to facilitate them.

Prediction of Stent-Retriever Thrombectomy Outcomes by Dynamic Multidetector CT Angiography in Patients with Acute Carotid T or MCA Occlusions.

BACKGROUND AND PURPOSE: The selection of patients for endovascular therapy is an important issue in stroke imaging. The aim of this study was to determine the predictive value of 3 different dynamic CT angiography parameters, occlusion length, collateralization extent, and time delay to maximum enhancement, for latest generation of stent retriever thrombectomy recanalization outcomes in patients with acute ischemic stroke. MATERIALS AND METHODS: In this study, subjects were selected from an initial cohort of 2059 consecutive patients who had undergone multiparametric CT, including whole-brain CT perfusion. We included all patients with a complete occlusion of the M1 segment of the MCA or the carotid T and subsequent intra-arterial stent retriever thrombectomy. Dynamic CT angiography was reconstructed from whole-brain CT perfusion raw datasets. Angiographic outcome was scored by using the modified TICI scale; and clinical outcome, by using the modified Rankin Scale. Logistic regression analyses were performed to determine independent predictors of a favorable angiographic (mTICI = 3) and clinical outcome (mRS ≤2). RESULTS: Sixty-nine patients (mean age, 68 ± 14 years; 46% men) were included for statistical analysis. In the regression analysis, a short occlusion length was an independent predictor of favorable angiographic outcome (OR, 0.41; P < .05). Both collateralization grade (OR, 1.00; P > .05) and time delay to peak enhancement (OR, 0.90; P > .05) failed to predict a favorable angiographic outcome. None of the dynamic CT angiography predictors were significantly associated with clinical outcome on discharge (OR, 0.664-1.011; P = .330-.953) or at 90 days (OR, 0.779-1.016; P = .130-.845). CONCLUSIONS: A short occlusion length as determined by dynamic CT angiography is an independent predictor of a favorable angiographic outcome of stent retriever thrombectomy in patients with ischemic stroke.