Subtraction of single-photon emission computed tomography (SPECT) in radioembolization: a comparison of four methods.

BACKGROUND: Subtraction of single-photon emission computed tomography (SPECT) images has a number of clinical applications in e.g. foci localization in ictal/inter-ictal SPECT and defect detection in rest/stress cardiac SPECT. In this work, we investigated the technical performance of SPECT subtraction for the purpose of quantifying the effect of a vasoconstricting drug (angiotensin-II, or AT2) on the Tc-99m-MAA liver distribution in hepatic radioembolization using an innovative interventional hybrid C-arm scanner. Given that subtraction of SPECT images is challenging due to high noise levels and poor resolution, we compared four methods to obtain a difference image in terms of image quality and quantitative accuracy. These methods included (i) image subtraction: subtraction of independently reconstructed SPECT images, (ii) projection subtraction: reconstruction of a SPECT image from subtracted projections, (iii) projection addition: reconstruction by addition of projections as a background term during the iterative reconstruction, and (iv) image addition: simultaneous reconstruction of the difference image and the subtracted image. RESULTS: Digital simulations (XCAT) and phantom studies (NEMA-IQ and anthropomorphic torso) showed that all four methods were able to generate difference images but their performance on specific metrics varied substantially. Image subtraction had the best quantitative performance (activity recovery coefficient) but had the worst visual quality (contrast-to-noise ratio) due to high noise levels. Projection subtraction showed a slightly better visual quality than image subtraction, but also a slightly worse quantitative accuracy. Projection addition had a substantial bias in its quantitative accuracy which increased with less counts in the projections. Image addition resulted in the best visual image quality but had a quantitative bias when the two images to subtract contained opposing features. CONCLUSION: All four investigated methods of SPECT subtraction demonstrated the capacity to generate a feasible difference image from two SPECT images. Image subtraction is recommended when the user is only interested in quantitative values, whereas image addition is recommended when the user requires the best visual image quality. Since quantitative accuracy is most important for the dosimetric investigation of AT2 in radioembolization, we recommend using the image subtraction method for this purpose.

Ablation of Small Liver Metastases Presenting as Foci of Diffusion Restriction on MRI-Results from the Prospective Minimally Invasive Thermal Ablation (MITA) Study.

PURPOSE: Liver metastases presenting as small hyperintense foci on diffusion-weighted imaging (DWI) pose a therapeutic challenge. Ablation is generally not possible since these lesions are often occult on ultrasound and CT. The purpose of this prospective study was to assess if small liver metastases (≤10 mm) detected on DWI can be successfully localized and ablated with the Hepatic Arteriography and C-Arm CT-Guided Ablation technique (HepACAGA). MATERIALS AND METHODS: All consecutive patients with small liver metastases (≤10 mm), as measured on DWI, referred for ablation with HepACAGA between 1 January 2021, and 31 October 2023, were included. Re-ablations and ablations concomitant with another local treatment were excluded. The primary outcome was the technical success rate, defined as the intraprocedural detection and subsequent successful ablation of small liver metastases using HepACAGA. Secondary outcomes included the primary and secondary local tumor progression (LTP) rates and the complication rate. RESULTS: A total of 15 patients (26 tumors) were included, with liver metastases from colorectal cancer (73%), neuro-endocrine tumors (15%), breast cancer (8%) and esophageal cancer (4%). All 26 tumors were successfully identified, punctured and ablated (a technical success rate of 100%). After a median follow-up of 9 months, primary and secondary LTP were 4% and 0%, respectively. No complications occurred. CONCLUSION: In this proof-of-concept study, the HepACAGA technique was successfully used to detect and ablate 100% of small liver metastases identified on DWI with a low recurrence rate and no complications. This technique enables the ablation of subcentimeter liver metastases detected on MRI.

[A young woman with hydronephrosis and ureteritis cystica]. / Een jonge vrouw met hydronefrose.

A 38-year-old woman with urosepsis and persistent unilateral hydronephrosis after antibiotic treatment. Antegrade pyelogram shows urine flow obstruction to the bladder. The whole ureter shows multiple small smooth-walled round lucent filling defects projecting into the lumen. The diagnosis ureteritis cystica was made.

Conventional versus Hepatic Arteriography and C-Arm CT-Guided Ablation of Liver Tumors (HepACAGA): A Comparative Analysis.

PURPOSE: Hepatic Arteriography and C-Arm CT-Guided Ablation of liver tumors (HepACAGA) is a novel technique, combining hepatic-arterial contrast injection with C-arm CT-guided navigation. This study compared the outcomes of the HepACAGA technique with patients treated with conventional ultrasound (US) and/or CT-guided ablation. MATERIALS AND METHODS: In this retrospective cohort study, all consecutive patients with hepatocellular carcinoma (HCC) or colorectal liver metastases (CRLM) treated with conventional US-/CT-guided ablation between 1 January 2015, and 31 December 2020, and patients treated with HepACAGA between 1 January 2021, and 31 October 2023, were included. The primary outcome was local tumor recurrence-free survival (LTRFS). Secondary outcomes included the local tumor recurrence (LTR) rate and complication rate. RESULTS: 68 patients (120 tumors) were included in the HepACAGA cohort and 53 patients (78 tumors) were included in the conventional cohort. In both cohorts, HCC was the predominant tumor type (63% and 73%, respectively). In the HepACAGA cohort, all patients received microwave ablation. Radiofrequency ablation was the main ablation technique in the conventional group (78%). LTRFS was significantly longer for patients treated with the HepACAGA technique (p = 0.015). Both LTR and the complication rate were significantly lower in the HepACAGA cohort compared to the conventional cohort (LTR 5% vs. 26%, respectively; p < 0.001) (complication rate 4% vs. 15%, respectively; p = 0.041). CONCLUSIONS: In this study, the HepACAGA technique was safer and more effective than conventional ablation for HCC and CRLM, resulting in lower rates of local tumor recurrence, longer local tumor recurrence-free survival and fewer procedure-related complications.

Hepatic Radioembolization: A Multistep Theragnostic Procedure.

This article provides a thorough overview of the practice and multistep approach of hepatic radioembolization. The current literature on hepatic radioembolization in primary or metastatic liver tumors as well as future perspectives are discussed.

The Added Value of Transcatheter CT Hepatic Angiography (CTHA) Image Guidance in Percutaneous Thermal Liver Ablation: An Experts' Opinion Pictorial Essay.

With the rapidly evolving field of image-guided tumor ablation, there is an increasing demand and need for tools to optimize treatment success. Known factors affecting the success of (non-)thermal liver ablation procedures are the ability to optimize tumor and surrounding critical structure visualization, ablation applicator targeting, and ablation zone confirmation. A recent study showed superior local tumor progression-free survival and local control outcomes when using transcatheter computed tomography hepatic angiography (CTHA) guidance in percutaneous liver ablation procedures. This pictorial review provides eight clinical cases from three institutions, MD Anderson (Houston, TX, USA), Gustave Roussy (Paris, France), and Amsterdam UMC (Amsterdam, The Netherlands), with the intent to demonstrate the added value of real-time CTHA guided tumor ablation for primary liver tumors and liver-only metastatic disease. The clinical illustrations highlight the ability to improve the detectability of the initial target liver tumor(s) and identify surrounding critical vascular structures, detect 'vanished' and/or additional tumors intraprocedurally, differentiate local tumor progression from non-enhancing scar tissue, and promptly detect and respond to iatrogenic hemorrhagic events. Although at the cost of adding a minor but safe intervention, CTHA-guided liver tumor ablation minimizes complications of the actual ablation procedure, reduces the number of repeat ablations, and improves the oncological outcome of patients with liver malignancies. Therefore, we recommend adopting CTHA as a potential quality-improving guiding method within the (inter)national standards of practice.

Impact of intraoperative imaging on decision-making during spine surgery: a survey among spine surgeons using simulated intraoperative images.

PURPOSE: To assess whether the intention to intraoperatively reposition pedicle screws differs when spine surgeons evaluate the same screws with 2D imaging or 3D imaging. METHODS: In this online survey study, 21 spine surgeons evaluated eight pedicle screws from patients who had undergone posterior spinal fixation. In a simulated intraoperative setting, surgeons had to decide if they would reposition a marked pedicle screw based on its position in the provided radiologic imaging. The eight assessed pedicle screws varied in radiologic position, including two screws positioned within the pedicle, two breaching the pedicle cortex < 2 mm, two breaching the pedicle cortex 2-4 mm, and two positioned completely outside the pedicle. Surgeons assessed each pedicle screw twice without knowing and in random order: once with a scrollable three-dimensional (3D) image and once with two oblique fluoroscopic two-dimensional (2D) images. RESULTS: Almost all surgeons (19/21) intended to reposition more pedicle screws based on 3D imaging than on 2D imaging, with a mean number of pedicle screws to be repositioned of, respectively, 4.1 (± 1.3) and 2.0 (± 1.3; p < 0.001). Surgeons intended to reposition two screws placed completely outside the pedicle, one breaching 2-4mm, and one breaching < 2 mm more often based on 3D imaging. CONCLUSION: When provided with 3D imaging, spine surgeons not only intend to intraoperatively reposition pedicle screws at risk of causing postoperative complications more often but also screws with acceptable positions. This study highlights the potential of intraoperative 3D imaging as well as the need for consensus on how to act on intraoperative 3D information.

Lung Mean Dose Prediction in Transarterial Radioembolization (TARE): Superiority of [166Ho]-Scout Over [99mTc]MAA in a Prospective Cohort Study.

PURPOSE: Radiation pneumonitis is a serious complication of radioembolization. In holmium-166 ([166Ho]) radioembolization, the lung mean dose (LMD) can be estimated (eLMD) using a scout dose with either technetium-99 m-macroaggregated albumin ([99mTc]MAA) or [166Ho]-microspheres. The accuracy of eLMD based on [99mTc]MAA (eLMDMAA) was compared to eLMD based on [166Ho]-scout dose (eLMDHo-scout) in two prospective clinical studies. MATERIALS AND METHODS: Patients were included if they received both scout doses ([99mTc]MAA and [166Ho]-scout), had a posttreatment [166Ho]-SPECT/CT (gold standard) and were scanned on the same hybrid SPECT/CT system. The correlation between eLMDMAA/eLMDHo-scout and LMDHo-treatment was assessed by Spearman's rank correlation coefficient (r). Wilcoxon signed rank test was used to analyze paired data. RESULTS: Thirty-seven patients with unresectable liver metastases were included. During follow-up, none developed symptoms of radiation pneumonitis. Median eLMDMAA (1.53 Gy, range 0.09-21.33 Gy) was significantly higher than median LMDHo-treatment (0.00 Gy, range 0.00-1.20 Gy; p < 0.01). Median eLMDHo-scout (median 0.00 Gy, range 0.00-1.21 Gy) was not significantly different compared to LMDHo-treatment (p > 0.05). In all cases, eLMDMAA was higher than LMDHo-treatment (p < 0.01). While a significant correlation was found between eLMDHo-scout and LMDHo-treatment (r = 0.43, p < 0.01), there was no correlation between eLMDMAA and LMDHo-treatment (r = 0.02, p = 0.90). CONCLUSION: [166Ho]-scout dose is superior in predicting LMD over [99mTc]MAA, in [166Ho]-radioembolization. Consequently, [166Ho]-scout may limit unnecessary patient exclusions and avoid unnecessary therapeutic activity reductions in patients eligible for radioembolization. TRAIL REGISTRATION: NCT01031784, registered December 2009. NCT01612325, registered June 2012.

Prophylactic Medication during Radioembolization in Metastatic Liver Disease: Is It Really Necessary? A Retrospective Cohort Study and Systematic Review of the Literature.

PURPOSE: Trans-arterial radioembolization is a well-studied tumoricidal treatment for liver malignancies; however, consensus and evidence regarding periprocedural prophylactic medication (PPM) are lacking. METHODS: A single-center retrospective analysis from 2014 to 2020 was performed in patients treated with 90Y-glass microspheres for neuroendocrine or colorectal liver metastases. Inclusion criteria were the availability of at least 3 months of clinical, biochemical, and imaging follow-up and post-treatment 90Y-PET/CT imaging for the determination of the whole non-tumorous liver absorbed dose (Dh). Logistic regression models were used to investigate if variables (among which are P/UDCA and Dh) were associated with either clinical toxicity, biochemical toxicity, or hepatotoxicity. Additionally, a structured literature search was performed in November 2022 to identify all publications related to PPM use in radioembolization treatments. RESULTS: Fifty-one patients received P/UDCA as post-treatment medication, while 19 did not. No correlation was found between toxicity and P/UDCA use. Dh was associated with biochemical toxicity (p = 0.05). A literature review resulted in eight relevant articles, including a total of 534 patients, in which no consistent advice regarding PPM was provided. CONCLUSION: In this single-center, retrospective review, P/UDCA use did not reduce liver toxicity in patients with metastatic liver disease. The whole non-tumorous liver-absorbed dose was the only significant factor for hepatotoxicity. No standardized international guidelines or supporting evidence exist for PPM in radioembolization.

Hepatic Arteriography and C-Arm CT-Guided Ablation (HepACAGA) to Improve Tumor Visualization, Navigation and Margin Confirmation in Percutaneous Liver Tumor Ablation.

PURPOSE: We present a technique that combines Hepatic Arteriography with C-arm CT-Guided Ablation (HepACAGA) to improve tumor visualization, navigation and margin confirmation for percutaneous ablation of liver tumors. MATERIALS AND METHODS: All consecutive patients scheduled for HepACAGA between April 20th, 2021, and November 2nd, 2021, were included in this retrospective, cohort study. HepACAGA was performed in an angiography-suite under general anesthesia. The hepatic artery was catheterized for selective contrast injection. C-arm CT and guidance software were then used to visualize the tumor and the microwave antenna was inserted during apnea. Pre- and post-ablation C-arm CTs were performed and ablation margins assessed. Technical success, antenna placement deviation, number of repositions, tumor recurrence, and safety were evaluated. Technical success was defined as a tumor that was ablated according to the HepACAGA technique. RESULTS: A total of 21 patients (28 tumors) were included. The main tumor type was colorectal cancer liver metastases (11/21, 52%), followed by hepatocellular carcinoma (7/21, 33%), neuroendocrine tumor metastases (1/21, 5%), and other tumor types (2/21, 10%). The technical success rate was 93% (26/28 tumors) with two small hypovascular lesions unable to be identified. A single microwave antenna was used in all patients. The median antenna placement deviation was 1 mm (range 0-6 mm). At a median follow-up time of 16 months (range 5-22 months), there was no tumor recurrence in any patient. Safety analysis showed a complication rate of 5% grade 2 and 5% grade 3. CONCLUSION: HepACAGA was demonstrated to be a safe and effective percutaneous ablation technique, without any local tumor recurrence in this study.

Dose finding study for unilobar radioembolization using holmium-166 microspheres to improve resectability in patients with HCC: the RALLY protocol.

BACKGROUND: High dose unilobar radioembolization (also termed 'radiation lobectomy')-the transarterial unilobar infusion of radioactive microspheres as a means of controlling tumour growth while concomitantly inducing future liver remnant hypertrophy-has recently gained interest as induction strategy for surgical resection. Prospective studies on the safety and efficacy of the unilobar radioembolization-surgery treatment algorithm are lacking. The RALLY study aims to assess the safety and toxicity profile of holmium-166 unilobar radioembolization in patients with hepatocellular carcinoma ineligible for surgery due to insufficiency of the future liver remnant. METHODS: The RALLY study is a multicenter, interventional, non-randomized, open-label, non-comparative safety study. Patients with hepatocellular carcinoma who are considered ineligible for surgery due to insufficiency of the future liver remnant (< 2.7%/min/m2 on hepatobiliary iminodiacetic acid scan will be included. A classical 3 + 3 dose escalation model will be used, enrolling three to six patients in each cohort. The primary objective is to determine the maximum tolerated treated non-tumourous liver-absorbed dose (cohorts of 50, 60, 70 and 80 Gy). Secondary objectives are to evaluate dose-response relationships, to establish the safety and feasibility of surgical resection following unilobar radioembolization, to assess quality of life, and to generate a biobank. DISCUSSION: This will be the first clinical study to assess the unilobar radioembolization-surgery treatment algorithm and may serve as a stepping stone towards its implementation in routine clinical practice. TRIAL REGISTRATION: Netherlands Trial Register NL8902 , registered on 2020-09-15.

Combining Selective Internal Radiation Therapy with Immunotherapy in Treating Hepatocellular Carcinoma and Hepatic Colorectal Metastases: A Systematic Review.

Background: Immunotherapy in the form of checkpoint inhibitors has changed the treatment paradigm in oncology. Combining selective internal radiation therapy (SIRT) with immunotherapy has been suggested to potentially improve outcomes in hepatocellular carcinoma (HCC) and metastatic colorectal carcinoma (mCRC). In this systematic review, the authors discuss the current developments and available clinical data regarding the combination of immunotherapy and SIRT in treating hepatic malignancies. Methods: PubMed, Embase, and Cochrane library were systematically searched for eligible studies (adhering to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines). Original patient studies written in English language with patients with HCC or mCRC who were treated with SIRT and immunotherapy were included. Endpoints evaluated included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Results: 1038 publications were screened, from which 1034 publications were excluded. Four studies with a total of 87 patients were included in this systematic review, of which two consisted of mCRC and the other two HCC. All four studies showed no increased toxicities of the combination therapy over known data on monotherapy. One mCRC study reported a median OS of 8 months, while the other mCRC study ended due to futility. Both reported an ORR of 0%. The two HCC studies reported a median OS of 16.5 and 16.2 months. Median PFS was 5.6 and 5.7 months. ORR ranged from 31% to 80%. Conclusion: The combination of SIRT and immunotherapy has been studied in four early-phase studies showing a favorable safety profile. Further studies are necessary to understand the possible synergy and possible benefit of combination therapy.

Current status of yttrium-90 microspheres radioembolization in primary and metastatic liver cancer.

Liver malignancy, including primary liver cancer and metastatic liver cancer, has become one of the most common causes of cancer-related death worldwide due to the high malignant degree and limited systematic treatment strategy. Radioembolization with yttrium-90 (90Y)-loaded microspheres is a relatively novel technology that has made significant progress in the local treatment of liver malignancy. The different steps in the extensive work-up of radioembolization for patients with an indication for treatment with 90Y microspheres, from patient selection to follow up, both technically and clinically, are discussed in this paper. It describes the application and development of 90Y microspheres in the treatment of liver cancer.

Assessing the accuracy of a new 3D2D registration algorithm based on a non-invasive skin marker model for navigated spine surgery.

PURPOSE: We assessed the accuracy of a new 3D2D registration algorithm to be used for navigated spine surgery and explored anatomical and radiologic parameters affecting the registration accuracy. Compared to existing 3D2D registration algorithms, the algorithm does not need bone-mounted or table-mounted instruments for registration. Neither does the intraoperative imaging device have to be tracked or calibrated. METHODS: The rigid registration algorithm required imaging data (a pre-existing CT scan (3D) and two angulated fluoroscopic images (2D)) to register positions of vertebrae in 3D and is based on non-invasive skin markers. The algorithm registered five adjacent vertebrae and was tested in the thoracic and lumbar spine from three human cadaveric specimens. The registration accuracy was calculated for each registered vertebra and measured with the target registration error (TRE) in millimeters. We used multivariable analysis to identify parameters independently affecting the algorithm's accuracy such as the angulation between the two fluoroscopic images (between 40° and 90°), the detector-skin distance, the number of skin markers applied, and waist circumference. RESULTS: The algorithm registered 780 vertebrae with a median TRE of 0.51 mm [interquartile range 0.32-0.73 mm] and a maximum TRE of 2.06 mm. The TRE was most affected by the angulation between the two fluoroscopic images obtained (p < 0.001): larger angulations resulted in higher accuracy. The algorithm was more accurate in thoracic vertebrae (p = 0.004) and in the specimen with the smallest waist circumference (p = 0.003). The algorithm registered all five adjacent vertebrae with similar accuracy. CONCLUSION: We studied the accuracy of a new 3D2D registration algorithm based on non-invasive skin markers. The algorithm registered five adjacent vertebrae with similar accuracy in the thoracic and lumbar spine and showed a maximum target registration error of approximately 2 mm. To further evaluate its potential for navigated spine surgery, the algorithm may now be integrated into a complete navigation system.

Safety and Efficacy of 166Ho Radioembolization in Hepatocellular Carcinoma: The HEPAR Primary Study.

The safety and efficacy of 166Ho radioembolization was first determined in the HEPAR and HEPAR II studies, which, however, excluded patients with hepatocellular carcinoma (HCC). The aim of this prospective clinical early phase II study was to establish the toxicity profile of 166Ho radioembolization in patients with measurable, liver-dominant HCC; Barcelona clinic liver cancer stage B or C; a Child-Pugh score of no more than B7; and an Eastern Cooperative Oncology Group performance status of 0-1 without curative treatment options. Methods: The primary endpoint was a rate of unacceptable toxicity defined as grade 3 hyperbilirubinemia (Common Terminology Cancer Adverse Events, version 4.03) in combination with a low albumin or ascites level in the absence of disease progression or treatment-related serious adverse events. Secondary endpoints included overall toxicity, response, survival, change in α-fetoprotein, and quality of life. Thirty-one patients with Barcelona clinic liver cancer stage B (71%) or C (29%) HCC were included, mostly multifocal (87%) or bilobar (55%) disease. Results: Common grade 1 or 2 clinical toxicity included fatigue (71%), back pain (55%), ascites (32%), dyspnea (23%), nausea (23%), and abdominal pain (23%), with no more than 10% grade 3-5 toxicity. Grade 3 laboratory toxicity (>10%) included an aspartate transaminase and γ-glutamyltransferase increase (16%), hyperglycemia (19%), and lymphopenia (29%). Treatment-related unacceptable toxicity occurred in 3 of 31 patients. At 3 mo, 54% of target lesions showed a complete or partial response according to modified RECIST. Median overall survival was 14.9 mo (95% CI, 10.4-24.9 mo). No significant changes in quality of life or pain were observed. Conclusion: The safety of 166Ho radioembolization was confirmed in HCC, with less than 10% unacceptable toxicity. Efficacy data support further evaluation.

Study Protocol PROMETHEUS: Prospective Multicenter Study to Evaluate the Correlation Between Safety Margin and Local Recurrence After Thermal Ablation Using Image Co-registration in Patients with Hepatocellular Carcinoma.

PURPOSE: The primary objective is to determine the minimal ablation margin required to achieve a local recurrence rate of < 10% in patients with hepatocellular carcinoma undergoing thermal ablation. Secondary objectives are to analyze the correlation between ablation margins and local recurrence and to assess efficacy. MATERIALS AND METHODS: This study is a prospective, multicenter, non-experimental, non-comparative, open-label study. Patients > 18 years with Barcelona Clinic Liver Cancer stage 0/A hepatocellular carcinoma (or B with a maximum of two lesions < 5 cm each) are eligible. Patients will undergo dual-phase contrast-enhanced computed tomography directly before and after ablation. Ablation margins will be quantitatively assessed using co-registration software, blinding assessors (i.e. two experienced radiologists) for outcome. Presence and location of recurrence are evaluated independently on follow-up scans by two other experienced radiologists, blinded for the quantitative margin analysis. A sample size of 189 tumors (~ 145 patients) is required to show with 80% power that the risk of local recurrence is confidently below 10%. A two-sided binomial z-test will be used to test the null hypothesis that the local recurrence rate is ≥ 10% for patients with a minimal ablation margin ≥ 2 mm. Logistic regression will be used to find the relationship between minimal ablation margins and local recurrence. Kaplan-Meier estimates are used to assess local and overall recurrence, disease-free and overall survival. DISCUSSION: It is expected that this study will result in a clear understanding of the correlation between ablation margins and local recurrence. Using co-registration software in future patients undergoing ablation for hepatocellular carcinoma may improve intraprocedural evaluation of technical success. Trial registration The Netherlands Trial Register (NL9713), https://www.trialregister.nl/trial/9713 .

Dose-Response and Dose-Toxicity Relationships for Glass 90Y Radioembolization in Patients with Liver Metastases from Colorectal Cancer.

Radioembolization based on personalized treatment planning requires established dose-response and dose-toxicity relationships. The aim of this study was to investigate dose-response and dose-toxicity relationships in patients with colorectal liver metastases (CRLMs) treated with glass 90Y-microspheres. Methods: All CRLM patients treated with glass 90Y-microspheres in our institution were retrospectively analyzed. The tumor-absorbed dose was calculated for each measurable metastasis (i.e.,18F-FDG-positive and more than a 5-cm3 tumor volume) on posttreatment 90Y PET. Metabolic tumor response was determined on 18F-FDG PET/CT by measuring the total lesion glycolysis at baseline and at 3 mo after treatment. The relationship between tumor-absorbed dose and metabolic response was determined on a per-lesion and per-patient basis using a linear mixed-effects regression model. Clinical toxicity and laboratory toxicity were correlated with healthy liver-absorbed dose. Results: Thirty-one patients were included. The median tumor-absorbed dose of 85 measurable metastases was 133 Gy (range, 20-1001 Gy). Per response category, this was 196 Gy for complete response (CR), 177 Gy for partial response (PR), 72 Gy for stable disease, and 95 Gy for progressive disease (PD). A significant dose-response relationship was found on a tumor level, with a significantly higher tumor-absorbed dose in metastases with CR (+94%) and PR (+74%) than in metastases with PD (P < 0.001). A similar relationship was found on a patient level, with PR having a higher tumor-absorbed dose than did PD (+58%, P = 0.044). A tumor-absorbed dose of more than 139 Gy predicted a 3-mo metabolic response with the greatest accuracy (89% specificity and 77% sensitivity), whereas a tumor-absorbed dose of more than 189 Gy predicted response with 97% specificity and 45% sensitivity. The median healthy liver-absorbed dose was 63 Gy (range, 24-113 Gy). Toxicity was limited mostly to grades 1 and 2, with 1 case of radioembolization-induced liver disease in a patient who received the highest healthy liver-absorbed dose. A positive trend was seen for most laboratory parameters in our dose-toxicity analysis. Conclusion: A significant relationship was observed between dose and response in CRLM patients treated with glass 90Y radioembolization.

Use of an anti-reflux catheter to improve tumor targeting for holmium-166 radioembolization-a prospective, within-patient randomized study.

PURPOSE: The objective of this study was to investigate whether the use of an anti-reflux catheter improves tumor targeting for colorectal cancer patients with unresectable, chemorefractory liver metastases (mCRC) treated with holmium-166 (166Ho)-radioembolization. MATERIALS AND METHODS: In this perspective, within-patient randomized study, left and right hepatic perfusion territories were randomized between infusion with a Surefire® anti-reflux catheter or a standard microcatheter. The primary outcome was the difference in tumor to non-tumor (T/N) activity distribution. Secondary outcomes included the difference in infusion efficiency, absorbed doses, predictive value of 166Ho-scout, dose-response relation, and survival. RESULTS: Twenty-one patients were treated in this study (the intended number of patients was 25). The median T/N activity concentration ratio with the use of the anti-reflux catheter was 3.2 (range 0.9-8.7) versus 3.6 (range 0.8-13.3) with a standard microcatheter. There was no difference in infusion efficiency (0.04% vs. 0.03% residual activity for the standard microcatheter and anti-reflux catheter, respectively) (95%CI - 0.05-0.03). No influence of the anti-reflux catheter on the dose-response rate was found. Median overall survival was 7.8 months (95%CI 6-13). CONCLUSION: Using a Surefire® anti-reflux catheter did not result in a higher T/N activity concentration ratio in mCRC patients treated with 166Ho-radioembolization, nor did it result in improved secondary outcomes measures. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT02208804.