To analyze changes in angiogenesis factors after transarterial radioembolization (TARE) with Yttrium- 90-loaded resin microspheres in hepatocellular carcinoma (HCC) patients.
Interleukin-6, interleukin-8, hepatocyte growth factor, platelet-derived growth factor, fibroblast growth factor, vascular endothelial growth factor-A (VEGF-A), and angiopoietin-2 levels in 26 patients were measured before TARE and on day 1, 7, 14, and 30 after TARE and evaluated regarding radiological response.
In the sixth month of follow-up, 11 (42.30%) patients had a complete or partial response to treatment, while progressive disease was found in 15 (57.69%) patients. The percentage changes in VEGF-A in the non-responders on day 30 (P = 0.034) after TARE were significantly more obvious. Peak formation rates of VEGF-A were higher in non-responders (P = 0.036).
Short-term changes in angiogenesis factors in HCC patients after TARE with Yttrium-90-loaded resin microspheres fluctuate with different amplitudes at different times. The upregulation of growth factors has a prognostic capacity. Changes in VEGF-A after TARE may be helpful for the early recognition of non-responders.

There is an increasing body of evidence indicating Y90 dose thresholds for tumor response and treatment-related toxicity. These thresholds are poorly studied in resin Y90, particularly in hepatocellular carcinoma (HCC).
To evaluate the efficacy of prospective voxel-based dosimetry for predicting treatment response and adverse events (AEs) in patients with HCC undergoing resin-based Y90 radioembolization.
This correlative study was based on a prospective single-arm clinical trial (NCT04172714), which evaluated the efficacy of low/scout (555 MBq) activity of resin-based Y90 for treatment planning. Partition model was used with goal of tumor dose (TD) > 200 Gy and non-tumoral liver dose (NTLD) < 70 Gy for non-segmental therapies. Single compartment dose of 200 Gy was used for segmentectomies. Prescribed Y90 activity minus scout activity was administered for therapeutic Y90 followed by Y90-PET/CT. Sureplan® (MIM Software, Cleveland, OH) was used for dosimetry analysis. Treatment response was evaluated at 3 and 6 months. Receiver operating characteristic curve determined TD response threshold for objective response (OR) and complete response (CR) as well as non-tumor liver dose (NTLD) threshold that predicted AEs.
N = 30 patients were treated with 33 tumors (19 segmental and 14 non-segmental). One patient died before the first imaging, and clinical follow-up was excluded from this analysis. Overall, 26 (81%) of the tumors had an OR and 23 (72%) had a CR. A mean TD of 253 Gy predicted an OR with 92% sensitivity and 83% specificity (area under the curve (AUC = 0.929, p < 0.001). A mean TD of 337 Gy predicted a CR with 83% sensitivity and 89% specificity (AUC = 0.845, p < 0.001). A mean NTLD of 81 and 87 Gy predicted grade 3 AEs with 100% sensitivity and 100% specificity in the non-segmental cohort at 3- and 6-month post Y90, respectively.
In patients with HCC undergoing resin-based Y90, there are dose response and dose toxicity thresholds directly affecting outcomes.
NCT04172714.

Dosimetry-guided treatment planning in selective internal radiation therapy relies on accurate and reproducible measurement of administered activity. This 4-center, 5-PET-device study compared the manufacturer-declared 90Y activity in vials with quantitative 90Y PET/CT assessment of the same vials. We compared 90Y PET-measured activity (APET) for 56 90Y-labeled glass and 18 90Y-labeled resin microsphere vials with the calibrated activity specified by the manufacturer (AM). Additionally, the same analysis was performed for 4 90Y-chloride vials. The mean APET/AM ratio was 0.79 ± 0.04 (range, 0.71-0.89) for glass microspheres and 1.15 ± 0.06 (range, 1.05-1.25) for resin microspheres. The mean APET/AM ratio for 90Y-chloride vials was 1.00 ± 0.04 (range, 0.96-1.06). Thus, we found an average difference of 46% between glass and resin microsphere activity calibrations, whereas close agreement was found for chloride solutions. We expect that the reported discrepancies will promote further investigations to establish reliable and accurate patient dosimetry and dose-effect assessments.

Primary liver tumours (i.e. hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC)) are among the most frequent cancers worldwide. However, only 10-20% of patients are amenable to curative treatment, such as resection or transplant. Liver metastases are most frequently caused by colorectal cancer, which accounts for the second most cancer-related deaths in Europe. In both primary and secondary tumours, radioembolization has been shown to be a safe and effective treatment option. The vast potential of personalized dosimetry has also been shown, resulting in markedly increased response rates and overall survival. In a rapidly evolving therapeutic landscape, the role of radioembolization will be subject to changes. Therefore, the decision for radioembolization should be taken by a multidisciplinary tumour board in accordance with the current clinical guidelines. The purpose of this procedure guideline is to assist the nuclear medicine physician in treating and managing patients undergoing radioembolization treatment. PREAMBLE: The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association that facilitates communication worldwide among individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. These guidelines are intended to assist practitioners in providing appropriate nuclear medicine care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals taking into account the unique circumstances of each case. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set out in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources or advances in knowledge or technology subsequent to publication of the guidelines. The practice of medicine involves not only the science but also the art of dealing with the prevention, diagnosis, alleviation and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognised that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.

Aim: To determine whether a liver tumor burden ≤25% and well-preserved liver function (albumin-bilirubin grade 1) are appropriate criteria for identifying patients with unresectable hepatocellular carcinoma who may benefit from selective internal radiation therapy (SIRT) using 90yttrium resin microspheres versus sorafenib. Patients & methods: Post-hoc analysis of patients in the intention-to-treat population of the SARAH trial (SIRT vs sorafenib) with ≤25% tumor burden and albumin-bilirubin grade 1. Primary end point: overall survival. Results: Median overall survival was 21.9 months (95% CI: 15.2-32.5, n = 37) with SIRT and 17.0 months (11.6-20.8, n = 48) with sorafenib (hazard ratios: 0.73; 95% CI: 0.44-1.21; p = 0.22). Conclusion: A combination of good liver function and low tumor burden may be relevant for selection of hepatocellular carcinoma patients for SIRT.

OBJECTIVE: Reported outcomes of patients with intra-hepatic cholangiocarcinoma (IH-CCA) treated with radioembolization are highly variable, which indicates differences in included patients\' characteristics and/or procedure-related variables. This study aimed to identify patient- and treatment-related variables predictive for radioembolization outcome.
METHODS: This retrospective multicenter study enrolled 58 patients with unresectable and chemorefractory IH-CCA treated with resin 90Y-microspheres. Clinicopathologic data were collected from patient records. Metabolic parameters of liver tumor(s) and presence of lymph node metastasis were measured on baseline 18F-FDG-PET/CT. 99mTc-MAA tumor to liver uptake ratio (TLRMAA) was computed for each lesion on the SPECT-CT. Activity prescription using body-surface-area (BSA) or more personalized partition-model was recorded. The study endpoint was overall survival (OS) starting from date of radioembolization. Statistical analysis was performed by the log-rank test and multivariate Cox\'s proportional hazards model.
RESULTS: Median OS (mOS) post-radioembolization of the entire cohort was 10.3 months. Variables associated with significant differences in terms of OS were serum albumin (hazard ratio (HR) = 2.78, 95%CI:1.29-5.98, p = 0.002), total bilirubin (HR = 2.17, 95%CI:1.14-4.12, p = 0.009), aspartate aminotransferase (HR = 2.96, 95%CI:1.50-5.84, p < 0.001), alanine aminotransferase (HR = 2.02, 95%CI:1.05-3.90, p = 0.01) and γ-GT (HR = 2.61, 95%CI:1.31-5.22, p < 0.001). The presence of lymph node metastasis as well as a TLRMAA < 1.9 were associated with shorter mOS: HR = 2.35, 95%CI:1.08-5.11, p = 0.008 and HR = 2.92, 95%CI:1.01-8.44, p = 0.009, respectively. Finally, mOS was significantly shorter in patients treated according to the BSA method compared to the partition-model: mOS of 5.5 vs 14.9 months (HR = 2.52, 95%CI:1.23-5.16, p < 0.001). Multivariate analysis indicated that the only variable that increased outcome prediction above the clinical variables was the activity prescription method with HR of 2.26 (95%CI:1.09-4.70, p = 0.03). The average mean radiation dose to tumors was significantly higher with the partition-model (86Gy) versus BSA (38Gy).
CONCLUSIONS: Radioembolization efficacy in patients with unresectable recurrent and/or chemorefractory IH-CCA strongly depends on the tumor radiation dose. Personalized activity prescription should be performed.

暂无摘要。

OBJECTIVE: Aim of the study was to evaluate the impact of parenchymal blood volume (PBV) C-arm CT in transarterial radioembolization (TARE) planning procedure regarding the appropriateness of segmental blood supply from selective catheter positions defined by angiographic images compared to PBV mapsto determine the influence of changed target volumes on dose calculation.
METHODS: A total of 22 consecutive patients (median age, 62 years) underwent a TARE planning procedure were included in this retrospective study. Selective angiograms and selective PBV C-arm CT (right and left liver lobe) were evaluated in a blinded fashion, regarding segmental hepatic artery variants. Volumetry of target volume and dosimetry of glass and resin microspheres were performed.
RESULTS: Classification of segment IV and segment I to the corresponding target vascular bed supply was correct in 91.0% (20/22) and 86.4% (19/22) for angiography and C-arm CT, respectively. Except one case, all other liver segments were classified properly to the left and right hepatic arterial supply. Based on the mismatch of the angiographic and the C-arm CT approach, changes of target volume were evident in 27.3% of patients, resulting in a mean mismatch volume of 90±54ml (range, 51-198ml) and a percentage of dose differences of 14.2±11.8% and 12.6±10.6% for the right and 12.5±8.5% and 11.1±7.8% for the left liver lobe in glass and resin microspheres, respectively.
CONCLUSIONS: The C-arm CT approach is superior to the angiographic determination of vascular supply of specific liver segments for dosimetry before radioembolization. Especially for unexperienced interventional radiologists or for a complex anatomy, C-arm CT improves individualized dosimetry concepts.

BACKGROUND: The purpose of this study is to evaluate the impact of switching from sterile water to 5 % glucose (G5W) for the administration of yttrium-90 ((90)Y)-resin microspheres on the total activity of (90)Y administered (expressed as a proportion of the prescribed/calculated activity), as well as the number of cases of stasis and the reported incidence of discomfort during the selective internal radiation therapy (SIRT) procedure.
METHODS: In December 2013, we switched from sterile water to G5W for the administration of SIRT using (90)Y resin microspheres in all patients. This retrospective observational single-center case series describes our experience in the months preceding and after the switch. Apart from the change in administration medium, the protocol for SIRT was otherwise identical.
RESULTS: One hundred and four SIRT procedures were performed on 78 patients (45 male, mean age: 63 years, range: 31-87 years) with either unresectable hepatocellular carcinoma, cholangiocarcinoma, or chemorefractory liver-dominant metastatic cancer. Compared with sterile water, the whole prescribed activity was administered in significantly more procedures with G5W: 85 vs. 22 %; p < 0.0001. A significantly higher proportion of the calculated activity was administered with G5W: 96.1 ± 11.0 % vs. 77.4 ± 24.3 % (p < 0.0001). G5W procedures were also associated with a significantly lower incidence of stasis (28 vs. 11 % procedures; p = 0.02) and mild-to-moderate upper abdominal pain during the procedure (1.8 vs. 44 % procedures; p < 0.0001).
CONCLUSIONS: Replacing sterile water with isotonic G5W during administration favorably impacts on the safety of SIRT, eliminates and/or minimizes flow reductions and stasis/reflux during administration of (90)Y resin microspheres, improves percentage activity delivered, and reduces peri-procedural pain.

(90)Y 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 (90)Y 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).
CONCLUSIONS: 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.