Dose-effect relationships in neuroendocrine tumour liver metastases treated with [166Ho]-radioembolization.

PURPOSE: Aim of this study was to investigate a dose-response relationship, dose-toxicity relationship, progression free survival (PFS) and overall survival (OS) in neuroendocrine tumour liver metastases (NELM) treated with holmium-166-microspheres radioembolization ([166Ho]-radioembolization). MATERIALS AND METHODS: Single center, retrospective study included patients with NELM that received [166Ho]-radioembolization with post-treatment SPECT/CT and CECT or MRI imaging for 3 months follow-up. Post-treatment SPECT/CT was used to calculate tumour (Dt) and whole liver healthy tissue (Dh) absorbed dose. Clinical and laboratory toxicity was graded by Common Terminology Criteria for Adverse Events (CTCAE), version 5 at baseline and three-months follow-up. Response was determined according to RECIST 1.1. The tumour and healthy doses was correlated to lesion-based objective response and patient-based toxicity. Kaplan Meier analyses were performed for progression free survival (PFS) and overall survival (OS). RESULTS: Twenty-seven treatments in 25 patients were included, with a total of 114 tumours. Median follow-up was 14 months (3 - 82 months). Mean Dt in non-responders was 68 Gy versus 118 Gy in responders, p = 0.01. ROC analysis determined 86 Gy to have the highest sensitivity and specificity, resp. 83% and 81%. Achieving a Dt of ≥ 120 Gy provided the highest likelihood of response (90%) for obtaining response. Sixteen patients had grade 1-2 clinical toxicity and only one patient grade 3. No clear healthy liver dose-toxicity relationship was found. The median PFS was 15 months (95% CI [10.2;19.8]) and median OS was not reached. CONCLUSION: This study confirms the safety and efficacy of [166Ho]-radioembolization in NELM in a real-world setting. A clear dose-response relationship was demonstrated and future studies should aim at a Dt of ≥ 120 Gy, being predictive of response. No dose-toxicity relationship could be established.

Accurate Placement and Revisions for Cervical Pedicle Screws Placed With or Without Navigation: A Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: To evaluate the accuracy of placement for cervical pedicle screws with and without the use of spinal navigation. METHODS: A structured search was conducted in electronic databases without any language or date restrictions. Eligible studies reported the proportion of accurately placed cervical pedicle screws measured on intraoperative or postoperative 3D imaging, and reported whether intraoperative navigation was used during screw placement. Randomized Studies (MINORS) criteria were used to evaluate the methodological quality of how accuracy was assessed for cervical pedicle screws. RESULTS: After screening and critical appraisal, 4697 cervical pedicle screws from 18 studies were included in the meta-analysis. The pooled proportion for cervical pedicle screws with a breach up to 2 mm was 94% for navigated screws and did not differ from the pooled proportion for non-navigated screws (96%). The pooled proportion for cervical pedicle screws placed completely in the pedicle was 76% for navigated screws and did not differ from the pooled proportion for non-navigated screws (82%). Intraoperative screw reposition rates and screw revision rates as a result of postoperative imaging also did not differ between navigated and non-navigated screw placement. CONCLUSIONS: This systematic review and meta-analysis found that the use of spinal navigation systems does not significantly improve the accuracy of placement of cervical pedicle screws compared to screws placed without navigation. Future studies evaluating intraoperative navigation for cervical pedicle screw placement should focus on the learning curve, postoperative complications, and the complexity of surgical cases.

Intra-arterial peptide-receptor radionuclide therapy for neuro-endocrine tumour liver metastases: an in-patient randomised controlled trial (LUTIA).

PURPOSE: Peptide receptor radionuclide therapy (PRRT) using [177Lu]Lu-DOTATATE has been shown to effectively prolong progression free survival in grade 1-2 gastroenteropancreatic neuroendocrine tumours (GEP-NET), but is less efficacious in patients with extensive liver metastases. The aim was to investigate whether tumour uptake in liver metastases can be enhanced by intra-arterial administration of [177Lu]Lu-DOTATATE into the hepatic artery, in order to improve tumour response without increasing toxicity. METHODS: Twenty-seven patients with grade 1-2 GEP-NET, and bi-lobar liver metastases were randomized to receive intra-arterial PRRT in the left or right liver lobe for four consecutive cycles. The contralateral liver lobe and extrahepatic disease were treated via a "second-pass" effect and the contralateral lobe was used as the control lobe. Up to three metastases (> 3 cm) per liver lobe were identified as target lesions at baseline on contrast-enhanced CT. The primary endpoint was the tumour-to-non-tumour (T/N) uptake ratio on the 24 h post-treatment [177Lu]Lu-SPECT/CT after the first cycle. This was calculated for each target lesion in both lobes using the mean uptake. T/N ratios in both lobes were compared using paired-samples t-test. FINDINGS: After the first cycle, a non-significant difference in T/N uptake ratio was observed: T/NIA = 17·4 vs. T/Ncontrol = 16·2 (p = 0·299). The mean increase in T/N was 17% (1·17; 95% CI [1·00; 1·37]). Of all patients, 67% (18/27) showed any increase in T/N ratio after the first cycle. CONCLUSION: Intra-arterial [177Lu]Lu-DOTATATE is safe, but does not lead to a clinically significant increase in tumour uptake.

Current Status and Future Direction of Hepatic Radioembolisation.

Radioembolisation is a locoregional treatment modality for hepatic malignancies. It consists of several stages that are vital to its success, which include a pre-treatment angiographic simulation followed by nuclear medicine imaging, treatment activity choice, treatment procedure and post-treatment imaging. All these stages have seen much advancement over the past decade. Here we aim to provide an overview of the practice of radioembolisation, discuss the limitations of currently applied methods and explore promising developments.

Systematic review of the safety and efficacy of contrast injection via venous catheters for contrast-enhanced computed tomography.

OBJECTIVE: To examine the safety and efficacy of contrast injection through a central venous catheter (CVC) for contrast-enhanced computed tomography (CECT). METHODS: A systematic literature search was performed using PubMed. Studies were deemed eligible if they reported on the use of CVCs for contrast administration. Selected articles were assessed for their relevance and risk of bias. Articles with low relevance and high risk of bias or both were excluded. Data from included articles was extracted. RESULTS: Seven studies reported on the use of CVCs for contrast administration. Catheter rupture did not occur in any study. The incidence of dislocation ranged from 2.2-15.4%. Quality of scans was described in three studies, with less contrast enhancement of pulmonary arteries and the thoracic aorta in two studies, and average or above average quality in one study. Four other studies used higher flowrates, but did not report quality of scans. CONCLUSION: Contrast injection via CVCs can be performed safely for CECT when using a strict protocol. Quality of scans depended on multiple factors like flow rate, indication of the scan, and cardiac output of the patient. In each patient, an individual evaluation whether to use the CVC as access for contrast media should be made, while bolus tracking may be mandatory in most cases.

Technical solutions to ensure safe yttrium-90 radioembolization in patients with initial extrahepatic deposition of (99m)technetium-albumin macroaggregates.

PURPOSE: To evaluate the incidence of extrahepatic deposition of technetium-99m-labeled albumin macroaggregates ((99m)Tc-MAA) after pretreatment angiography, before yttrium-90 radioembolizaton ((90)Y-RE), and to report on technical solutions that can be used to ensure safe delivery of (90)Y-microspheres in patients with initial extrahepatic deposition. MATERIALS AND METHODS: A retrospective analysis of 26 patients with primary and secondary liver malignancies, who were scheduled for treatment with (90)Y-RE in our institution in 2009, was performed. The angiograms and single-photon emission computed tomography images of all patients were reviewed by an interventional radiologist and a nuclear medicine physician, respectively, to identify and localize extrahepatic deposition of (99m)Tc-MAA when present. Subsequently, the technical solutions were used to successfully perform (90)Y-RE in these patients were evaluated and described. RESULTS: Extrahepatic deposition of (99m)Tc-MAA was observed in 8 of 26 patients (31%). In 7 of 8 patients, a second pretreatment angiography was performed to detect the cause of extrahepatic deposition. The technical solutions to enable safe (90)Y microspheres delivery included more distal placement of the microcatheter in the proper/right hepatic artery in 4 of 7 (57%) patients; (super)selective catheterization of multiple segmental branches in 2 of 7 (29%); and additional coiling of a newly detected branch in the remaining patient (14%). This was confirmed by a second MAA procedure. (90)Y-RE was eventually performed in 25 of 26 (96%) patients. No procedure-related complications (<30 days) were observed. CONCLUSION: Extrahepatic deposition of (99m)Tc-MAA after pretreatment angiography did occur in 8 of 26 (31%) patients. The technical solutions as presented allowed safe (90)Y-RE delivery in 25 of 26 (96%) patients.