Arthur J. A. T. Braat

The Efficacy of Hepatic 90Y Resin Radioembolization for Metastatic Neuroendocrine Tumors: A Meta-Analysis

90Y resin radioembolization is an emerging treatment in patients with liver-dominant metastatic neuroendocrine tumors (mNETs), despite the absence of level I data. The aim of this study was to evaluate the efficacy of this modality in a meta-analysis of the published literature. Methods: A comprehensive review protocol screened all reports in the literature. Strict selection criteria were applied to ensure consistency among the selected studies: human subjects, complete response data with time interval, resin microspheres, more than 5 patients, not a duplicate cohort, English language, and separate and complete data for resin-based 90Y treatment of mNET if the study included multiple tumor and microsphere types. Selected studies were critically appraised on 50 study criteria, in accordance with the research reporting standards for radioembolization. Response data (Response Evaluation Criteria in Solid Tumors) were extracted and analyzed using both fixed and random-effects meta-analyses. Results: One hundred fifty-six studies were screened; 12 were selected, totaling 435 procedures for response assessment. Funnel plots showed no evidence of publication bias (P = 0.841). Critical appraisal revealed a median of 75% of desired criteria included in selected studies. Very high between-study heterogeneity ruled out a fixed-effects model. The random-effects weighted average objective response rate (complete and partial responses, CR and PR, respectively) was 50% (95% confidence interval, 38%–62%), and weighted average disease control rate (CR, PR, and stable disease) was 86% (95% confidence interval, 78%–92%). The percentage of patients with pancreatic mNET was marginally associated with poorer response (P = 0.030), accounting for approximately 23% of the heterogeneity among studies. The percentage of CR and PR correlated with median survival (R = 0.85; P = 0.008). Conclusion: This meta-analysis confirms radioembolization to be an effective treatment option for patients with hepatic mNET. The pooled data demonstrated a high response rate and improved survival for patients responding to therapy.

⁹⁰Y Hepatic Radioembolization : An Update on Current Practice and Recent Developments

Radioembolization is an established treatment modality that has been subjected to many improvements over the last decade. Developments are occurring at a high pace, affecting patient selection and treatment. The aim of this review is therefore to provide an overview of current practice, with a focus on recent developments in the field of radioembolization. Several practical issues and recommendations in the application of radioembolization will be discussed, ranging from patient selection to treatment response and future applications.

Hepatic Radioembolization as a Bridge to Liver Surgery

Treatment of oncologic disease has improved significantly in the last decades and in the future a vast majority of cancer types will continue to increase worldwide. As a result, many patients are confronted with primary liver cancers or metastatic liver disease. Surgery in liver malignancies has steeply improved and curative resections are applicable in wider settings, leading to a prolonged survival. Simultaneously, radiofrequency ablation (RFA) and liver transplantation (LTx) have been applied more commonly in oncologic settings with improving results. To minimize adverse events in treatments of liver malignancies, locoregional minimal invasive treatments have made their appearance in this field, in which radioembolization (RE) has shown promising results in recent years with few adverse events and high response rates. We discuss several other applications of RE for oncologic patients, other than its use in the palliative setting, whether or not combined with other treatments. This review is focused on the role of RE in acquiring patient eligibility for radical treatments, like surgery, RFA, and LTx. Inducing significant tumor reduction can downstage patients for resection or, through attaining stable disease, patients can stay on the LTx waiting list. Hereby, RE could make a difference between curative of palliative intent in oncologic patient management. Prior to surgery, the future remnant liver volume might be inadequate in some patients. In these patients, forming an adequate liver reserve through RE leads to prolonged survival without risking post-operative liver failure and minimizing tumor progression while inducing hypertrophy. In order to optimize results, developments in procedures surrounding RE are equally important. Predicting the remaining liver function after radical treatment and finding the right balance between maximum tumor irradiation and minimizing the chance of inducing radiation-related complications are still challenges.

Impact of external cooling with icepacks on 68Ga-PSMA uptake in salivary glands

BackgroundExternal cooling of the salivary glands is advised to prevent xerostomia in lutetium-177-PSMA treatment for advanced prostate cancer. Since evidence addressing this subject is sparse, this study aims to determine impact of icepacks application on uptake in salivary glands. Eighty-nine patients referred for gallium-68-PSMA PET/CT for (re)staging of prostate cancer were prospectively included. Twenty-four patients were scanned with unilateral (solely left-sided) icepacks; 20 with bilateral icepacks; 45 without icepacks. Icepacks were applied approximately 30 minutes prior to tracer injection. PET/CT acquisition started 1 hour postinjection. Radiotracer uptake was measured in the parotid- and submandibular glands.ResultsWhen comparing the intervention group with the control group, uptake in the left parotid gland significantly differed: SUVmax: 11.07 ± 3.53 versus 12.95 ± 4.16; p = 0.02. SUVpeak: 9.91 ± 3.14 versus 11.45 ± 3.61; p = 0.04. SUVmax and SUVpeak were reduced with 14.52% and 13.45%. All other SUV values did not significantly differ. Patients with bilateral icepacks showed no significant differences in PSMA uptake compared to the control group (all: p > 0.05). Intra-patient analysis revealed some significant differences in SUVmax and SUVpeak between the cooled and non-cooled parotid gland (SUVmax: 11.12 ± 3.71 versus 12.69 ± 3.75; p = 0.00. SUVpeak: 9.93 ± 3.32 versus 11.25 ± 3.25; p = 0.00).ConclusionsImpact of icepacks on PSMA uptake seems to be limited to the parotid glands. As clinical relevance of these findings is debatable, structural application of icepacks in the setting of lutetium-177 PSMA therapy needs careful consideration.

Estimation of lung shunt fraction from simultaneous fluoroscopic and nuclear images

Radioembolisation with yttrium-90 (90Y) is increasingly used as a treatment of unresectable liver malignancies. For safety, a scout dose of technetium-99m macroaggregated albumin (99mTc-MAA) is used prior to the delivery of the therapeutic activity to mimic the deposition of 90Y. One-day procedures are currently limited by the lack of nuclear images in the intervention room. To cope with this limitation, an interventional simultaneous fluoroscopic and nuclear imaging device is currently being developed. The purpose of this simulation study was to evaluate the accuracy of estimating the lung shunt fraction (LSF) of the scout dose in the intervention room with this device and compare it against current clinical methods. METHODS A male and female XCAT phantom, both with two respiratory profiles, were used to simulate various LSFs resulting from a scout dose of 150 MBq 99mTc-MAA. Hybrid images were Monte Carlo simulated for breath-hold (5 s) and dynamic breathing (10 frames of 0.5 s) acquisitions. Nuclear images were corrected for attenuation with the fluoroscopic image and for organ overlap effects using a pre-treatment CT-scan. For comparison purposes, planar scintigraphy and mobile gamma camera images (both 300 s acquisition time) were simulated. Estimated LSFs were evaluated for all methods and compared to the phantom ground truth. RESULTS In the clinically relevant range of 10-20% LSF, hybrid imaging overestimated LSF with approximately 2 percentage points (pp) and 3 pp for the normal and irregular breathing phantoms, respectively. After organ overlap correction, LSF was estimated with a more constant error. Errors in planar scintigraphy and mobile gamma camera imaging were more dependent on LSF, body shape and breathing profile. CONCLUSION LSF can be estimated with a constant minor error with a hybrid imaging device. Estimated LSF is highly dependent on true LSF, body shape and breathing pattern when estimated with current clinical methods. The hybrid imaging device is capable of accurately estimating LSF within a few seconds in an interventional setting.

The physics of radioembolization

Radioembolization is an established treatment for chemoresistant and unresectable liver cancers. Currently, treatment planning is often based on semi-empirical methods, which yield acceptable toxicity profiles and have enabled the large-scale application in a palliative setting. However, recently, five large randomized controlled trials using resin microspheres failed to demonstrate a significant improvement in either progression-free survival or overall survival in both hepatocellular carcinoma and metastatic colorectal cancer. One reason for this might be that the activity prescription methods used in these studies are suboptimal for many patients.In this review, the current dosimetric methods and their caveats are evaluated. Furthermore, the current state-of-the-art of image-guided dosimetry and advanced radiobiological modeling is reviewed from a physics’ perspective. The current literature is explored for the observation of robust dose-response relationships followed by an overview of recent advancements in quantitative image reconstruction in relation to image-guided dosimetry.This review is concluded with a discussion on areas where further research is necessary in order to arrive at a personalized treatment method that provides optimal tumor control and is clinically feasible.