Early-Stage HCC Percutaneous Locoregional Management: East versus West Perspectives.

Hepatocellular carcinoma represents an important cause of death worldwide. Early-stage hepatocellular carcinoma patients not suitable for surgery can be treated with a variety of minimally invasive locoregional interventional oncology techniques. Various guidelines in different countries address the treatment of hepatocellular carcinoma, but the actual treatment is usually discussed by a multidisciplinary tumor board in a personalized manner, leading to potential treatment differences based on Western and Eastern perspectives. The aim of this paper is to integrate literature evidence with the eminent experiences collected during a focused session at the Mediterranean Interventional Oncology (MIO) Live Congress 2023.

Combination of ablation and embolization for intermediate-sized liver metastases from colorectal cancer: what can we learn from treating primary liver cancer?

Colorectal cancer liver metastases (CRLMs) are common. Treating CRLMs with thermal ablation can prolong survival, but compared to lesions smaller than 3 cm, local control rates and overall survival are relatively worse with larger, intermediate (3-5 cm) lesions. Local recurrence rates range between 1.7%-20.2% and 6.7%-68.9% for CRLMs less than 3 cm and greater than 3 cm, respectively. Worse outcomes are also present when ablating intermediate size hepatocellular carcinoma (HCC) and there are some pathological similarities with CRLMs, namely the presence of micrometastatic disease. Combining ablation with transarterial chemoembolization is more effective in treating intermediate-size HCC than ablation alone. A meta-analysis of robust randomized controlled trials demonstrated long-term improved survival with combination therapy compared to ablation alone (odds ratio at 1, 3 and 5 years of 2.74, 2.77 and 5.23, respectively). There is, however, minimal evidence for combination therapy in CRLMs, limited to a handful of studies that are predominantly retrospective and have heterogeneous inclusion criteria. Given the difficulty in successfully treating intermediate CRLMs, the strong evidence for combination therapy in intermediate HCC and potential pathological similarities, formal evaluation of combination treatment in CRLM is merited. This review highlights existing evidence for treatment of intermediate-size liver lesions and highlights where trials in CRLMs should focus.

Radioembolisation in patients with hepatocellular carcinoma that have previously received liver-directed therapies.

PURPOSE: Radioembolisation is part of the multimodal treatment of hepatocellular carcinoma (HCC) at specialist liver centres. This study analysed the impact of prior treatment on tolerability and survival following radioembolisation. METHODS: This was a retrospective analysis of 325 consecutive patients with a confirmed diagnosis of HCC, who received radioembolisation with yttrium-90 resin microspheres at eight European centres between September 2003 and December 2009. The decision to treat was based on the clinical judgement of multidisciplinary teams. Patients were followed from the date of radioembolisation to last contact or death and the nature and severity of all adverse events (AEs) recorded from medical records. RESULTS: Most radioembolisation candidates were Child-Pugh class A (82.5%) with multinodular HCC (75.9%) invading both lobes (53.1%); 56.3% were advanced stage. Radioembolisation was used first-line in 57.5% of patients and second-line in 34.2%. Common prior procedures were transarterial (chemo)embolisation therapies (27.1%), surgical resection/transplantation (17.2%) and ablation (8.6%). There was no difference in AE incidence and severity between prior treatment subgroups. Median (95% confidence interval [CI]) survival following radioembolisation was similar between procedure-naive and prior treatment groups for Barcelona Clinic Liver Cancer (BCLC) stage A: 22.1 months (15.1-45.9) versus 30.9 months (19.6-46.8); p = 0.243); stage B: 18.4 months (11.2-19.4) versus 22.8 months (10.9-34.2); p = 0.815; and stage C: 8.8 months (7.1-10.8) versus 10.8 months (7.7-12.6); p = 0.976. CONCLUSIONS: Radioembolisation is a valuable treatment option for patients who relapse following surgical, ablative or vascular procedures and remain suitable candidates for this treatment.

Efficacy and Safety of Drug Eluting Bead TACE with Microspheres <150 µm for the Treatment of Hepatocellular Carcinoma.

BACKGROUND/AIM: To retrospectively evaluate the efficacy and safety of drug eluting bead (DEB) transarterial chemoembolisation (TACE) with microspheres <150 µm for the treatment of hepatocellular carcinoma (HCC) with respect to overall survival, progression-free survival, tumor response and the peri-interventional toxicity. MATERIALS AND METHODS: In this retrospective, single-center study we analyzed 32 HCC-patients (BCLC A: 10 patients, BCLC B: 17 patients, BCLC C: 5 patients), who were treated with (DEB) <15 µm (DCBeadM1®) loaded with epirubicin between 2011 and 2015. We analyzed MRI and CT-scans as well as blood results like AFP, bilirubin and liver enzymes before (t0) and after (t1=first follow-up, t2=last follow-up within 6 months) locoregional treatment. The tumor response was evaluated by MRI and CT considering m-RECIST and the EASL-criteria as well as alpha-fetoprotein (AFP) levels in the peripheral blood. RESULTS: We found a significant tumor response at all follow-up times (p<0.05) according to m-RECIST criteria and a significant tumor response between t0 vs. t1 (p<0.05) and t0 vs. t2 (p<0.05) according to EASL criteria. We observed a significant decrease of the AFP-level between t0 and t1. The objective response rates (ORR) of target lesions were 64.3% and 78.5 % corresponding to m-RECIST and EASL, respectively. The median overall survival (OS) was 30.5 months, the progression-free survival in relation to the target lesion was 14.3 months by using m-RECIST and EASL criteria. In the period of 30 days after treatment we found no grade 5 adverse events (AE). During the follow-up period 1 abscess (3.7%) was observed. In a total of 5 patients, 4 (14.7%) biliomas with no need of treatment and 3 (10.7%) widening of the intrahepatic bile ducts were noted. CONCLUSION: The use of DEB <150 µm (DCBeadM1®) shows promising results in the treatment of HCC without showing substantial hepatic toxicity, but some widening of the intrahepatic bile ducts and one abscess. Further trials are necessary to evaluate the efficacy and toxicity of DEB-TACE with M1®-beads.

Safety, Efficacy, and Prognostic Factors After Radioembolization of Hepatic Metastases from Breast Cancer: A Large Single-Center Experience in 81 Patients.

UNLABELLED: The present study evaluated safety, efficacy, and prognostic factors for (90)Y-yttrium microsphere radioembolization of unresectable liver metastases from breast cancer. METHODS: Eighty-one patients were treated with radioembolization. Acute toxicity was monitored through daily physical examination and serum tests until 3 d after radioembolization; late toxicity was evaluated until 12 wk after radioembolization. Overall survival and response according to (18)F-FDG PET (>30% decrease of tracer uptake) and CA15-3 serum level (any decline) were recorded. Pretherapeutic characteristics, including pretreatment history, liver function tests, and PET/CT parameters, were assessed by univariate and subsequent multivariate Cox regression for predicting patient survival. RESULTS: A toxicity grade of 3 or more based on clinical symptoms, bilirubin, ulcer, pancreatitis, ascites, or radioembolization-induced liver disease occurred in 10% or less of patients. Two patients eventually died from radioembolization-induced liver disease. Sequential lobar treatment and absence of prior angiosuppressive therapy were both associated with a lower rate of serious adverse events. On the basis of PET/CA15-3 criteria, 52/61% of patients responded to treatment. Median overall survival after radioembolization was 35 wk (interquartile range, 41 wk). Pretherapeutic tumor burden of the liver greater than 50% or more (P< 0.001; hazard ratio, 5.67; 95% confidence interval, 2.41-13.34) and a transaminase toxicity grade of 2 or more (P= 0.009; hazard ratio, 2.15; 95% confidence interval, 1.21-3.80) independently predicted short survival. CONCLUSION: Radioembolization for breast cancer liver metastases shows encouraging local response rates with low incidence of serious adverse events, especially in those patients with sequential lobar treatment or without prior angiosuppressive therapy. High hepatic tumor burden and liver transaminase levels at baseline indicate poor outcome.

Predictive Value of 99mTc-MAA SPECT for 90Y-Labeled Resin Microsphere Distribution in Radioembolization of Primary and Secondary Hepatic Tumors.

UNLABELLED: This study analyzed the predictive value of (99m)Tc-labeled macroaggregated albumin ((99m)Tc-MAA) SPECT for (90)Y-labeled resin microsphere therapy (radioembolization) by comparing uptake on pretherapeutic (99m)Tc-MAA SPECT with uptake on posttherapeutic (90)Y-bremsstrahlung SPECT. METHODS: We included 502 patients (55% male; mean age ± SD, 62 ± 11 y) who underwent radioembolization between 2005 and 2013 because of primary or secondary liver malignancies (colorectal cancer [n = 195, 38.8%], neuroendocrine tumors [n = 77, 15.3%], breast cancer [n = 68, 13.5%], hepatocellular carcinoma [n = 59, 11.8%], cholangiocellular carcinoma [n = 40, 8.0%], or urologic tumors [n = 14, 2.8%]). Manually drawn regions of interest around tumors and adjacent healthy liver tissue for up to 3 lesions per patient on (99m)Tc-MAA and (90)Y-bremsstrahlung scans were used to quantify mean counts per pixel and evaluate the mean tumor-to-background ratio (TBR). Data were given as mean ± SD. Additionally, uptake in lesions on (99m)Tc-MAA and (90)Y-bremsstrahlung scans was graded visually as homogeneously higher than (grade 1), heterogeneously higher than (grade 2), equal to (grade 3), or lower than (grade 4) uptake in normal liver tissue. The Mann-Whitney U test and Spearman correlation were used to evaluate statistically significant differences between (99m)Tc-MAA and (90)Y-bremsstrahlung SPECT. RESULTS: In total, 1,008 lesions were analyzed. Of the 23% (230/1,008) of lesions that had grade 1 uptake on (99m)Tc-MAA SPECT, 81% (186/230) remained grade 1 after radioembolization whereas 16% (37/230) were grade 2. Of the lesions with grade 2 uptake on (99m)Tc-MAA SPECT, 16% had grade 1 uptake and 82% grade 2 uptake after radioembolization. Of the lesions with grade 3 uptake, however, 27% had grade 1 uptake and 47% grade 2 uptake after radioembolization. Even among the lesions with grade 4 uptake on (99m)Tc-MAA SPECT, 21% had grade 1 uptake and 46% grade 2 uptake after radioembolization. The mean TBR on (99m)Tc-MAA and (90)Y-bremsstrahlung SPECT showed a significant, though low, correlation in the total population (r = 0.26; P < 0.001) and in hepatocellular carcinoma (r = 0.4; P < 0.001), cholangiocellular carcinoma (r = 0.3; P < 0.05), breast cancer (r = 0.3; P < 0.001), colorectal cancer (r = 0.2; P < 0.001), and neuroendocrine tumors (r = 0.2; P < 0.01). CONCLUSION: Although significant for most lesions, the correlation between (99m)Tc-MAA and (90)Y-microsphere mean TBR was low. Classifying uptake into 4 grades revealed that lesions with high uptake on (99m)Tc-MAA SPECT maintain high uptake within radioembolization. More than 60% of lesions with a pretherapeutically lower uptake than in healthy liver tissue, however, showed high uptake within radioembolization. Patients with low tumor uptake on pretherapeutic (99m)Tc-MAA imaging should not be excluded from radioembolization.

Systematic evaluation of tumoral 99mTc-MAA uptake using SPECT and SPECT/CT in 502 patients before 90Y radioembolization.

UNLABELLED: The aim of this study was to evaluate the (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) uptake of primary and secondary liver tumors in a large patient cohort before (90)Y radioembolization. METHODS: We included 502 patients during the years 2005-2013 (55% male; mean age, 62 ± 11 y), who were examined with (99m)Tc-MAA SPECT or SPECT/CT before planned radioembolization. The patients had colorectal cancer (CRC; n = 195, 38.8%), neuroendocrine tumors (NET; n = 77, 15.3%), mammary cancer (MAM; n = 68, 13.5%), hepatocellular carcinoma (HCC; n = 59, 11.8%), cholangiocellular carcinoma (CCC; n = 40, 8.0%), or urologic tumors (URO; n = 14, 2.8%). SPECT with coregistered contrast-enhanced CT or MR imaging and SPECT/CT images of these patients were analyzed using dedicated software with regard to the (99m)Tc-MAA uptake of the liver tumors. Regions of interest were drawn around the lesions manually and quantified the uptake of up to 3 lesions per patient and also adjacent healthy liver tissue without evidence of tumor. We quantified maximum and mean counts per pixel and calculated tumor-to-background ratio (TBR). Data are reported as mean ± SD. Lesion uptake was classified as being homogeneously high (grade 1), heterogeneously high (grade 2), equal to that of the liver (grade 3), or low (grade 4). RESULTS: Grade 1 uptake was seen in 230 of 1,008 lesions (with the highest rates in sarcoma [47%], MAM [37%], and NET [32%]), grade 2 in 706 lesions (with the highest rates in CRC [77%], HCC [75%], and CCC [74%]), grade 4 in 57 lesions (with the highest rates in pancreatic cancer [17%], sarcoma [SAR] [13%], and MAM [8%]), and grade 3 in only 15 lesions. In quantitative analysis, the mean TBRmax of all lesions was 4.8 ± 4.1 (range, 0.2-50.1), with the highest values in HCC (6.0 ± 4.7; range, 1.4-21.6), NET (5.4 ± 4.9; range, 0.8-43.0), pancreatic cancer (4.0 ± 2.8; range, 0.9-12.2), and CCC (4.7 ± 2.9; range, 0.9-11.6), and the lowest values in SAR (3.5 ± 1.8; range, 0.8-2.7) and MAM (3.6 ± 2.2; range, 0.9-11.6). The mean TBRmean was 1.9 ± 1.0 (range, 0.1-7.2), with the highest values in NET (2.2 ± 1.2; range, 0.2-7.2), HCC (2.1 ± 1.2; range, 0.3-6.3), and CCC (2.0 ± 1.0; range, 0.2-6.3) and the lowest values in MAM (1.7 ± 0.8; range, 0.2-4.1), CRC (1.8 ± 0.9; range, 0.4-6.6), and SAR (1.7 ± 1.1; range, 0.3-3.9). CONCLUSION: The (99m)Tc-MAA uptake of different tumor entities shows a wide variation, with generally highest values for NET, HCC, and CCC and lowest values for MAM, CRC, and SAR. However, the variation of uptake within the different tumor entities is high.

Nomogram including pretherapeutic parameters for prediction of survival after SIRT of hepatic metastases from colorectal cancer.

OBJECTIVES: Pre-therapeutic prediction of outcome is important for clinicians and patients in determining whether selective internal radiation therapy (SIRT) is indicated for hepatic metastases of colorectal cancer (CRC). METHODS: Pre-therapeutic characteristics of 100 patients with colorectal liver metastases (CRLM) treated by radioembolization were analyzed to develop a nomogram for predicting survival. Prognostic factors were selected by univariate Cox regression analysis and subsequent tested by multivariate analysis for predicting patient survival. The nomogram was validated with reference to an external patient cohort (n = 25) from the Bonn University Department of Nuclear Medicine. RESULTS: Of the 13 parameters tested, four were independently associated with reduced patient survival in multivariate analysis. These parameters included no liver surgery before SIRT (HR:1.81, p = 0.014), CEA serum level ≥ 150 ng/ml (HR:2.08, p = 0.001), transaminase toxicity level ≥2.5× upper limit of normal (HR:2.82, p = 0.001), and summed computed tomography (CT) size of the largest two liver lesions ≥10 cm (HR:2.31, p < 0.001). The area under the receiver-operating characteristic curve for our prediction model was 0.83 for the external patient cohort, indicating superior performance of our multivariate model compared to a model ignoring covariates. CONCLUSIONS: The nomogram developed in our study entailing four pre-therapeutic parameters gives good prediction of patient survival post SIRT. KEY POINTS: • Four individual parameters predicted reduced survival following SIRT in CRC. • These parameters were combined into a nomogram of pre-therapeutic risk stratification. • The model provided good prediction of survival in two independent patient cohorts.

Pilot randomized trial of selective internal radiation therapy vs. chemoembolization in unresectable hepatocellular carcinoma.

BACKGROUND & AIMS: To compare selective internal radiation therapy (SIRT) with transarterial chemoembolization (TACE), the standard-of-care for intermediate-stage unresectable, hepatocellular carcinoma (HCC), as first-line treatment. METHODS: SIRTACE was an open-label multicenter randomized-controlled pilot study, which prospectively compared primarily safety and health-related quality of life (HRQoL) changes following TACE and SIRT. Patients with unresectable HCC, Child-Pugh ≤B7, ECOG performance status ≤2 and ≤5 liver lesions (≤20 cm total maximum diameter) without extrahepatic spread were randomized to receive either TACE (at 6-weekly intervals until tumour enhancement was not observed on MRI or disease progression) or single-session SIRT (yttrium-90 resin microspheres). RESULTS: Twenty-eight patients with BCLC stage A (32.1%), B (46.4%) or C (21.4%) received either a mean of 3.4 (median 2) TACE interventions (N = 15) or single SIRT (N = 13). Both treatments were well tolerated. Despite SIRT patients having significantly worse physical functioning at baseline, at week-12, neither treatment had a significantly different impact on HRQoL as measured by Functional Assessment of Cancer Therapy-Hepatobiliary total or its subscales. Both TACE and SIRT were effective for the local control of liver tumours. Best overall response-rate (RECIST 1.0) of target lesions were 13.3% and 30.8%, disease control rates were 73.3% and 76.9% for TACE and SIRT, respectively. Two patients in each group were down-staged for liver transplantation (N = 3) or radiofrequency ablation (N = 1). CONCLUSIONS: Single-session SIRT appeared to be as safe and had a similar impact on HRQoL as multiple sessions of TACE, suggesting that SIRT might be an alternative option for patients eligible for TACE.

CT fluoroscopy-guided percutaneous fiducial marker placement for CyberKnife stereotactic radiosurgery: technical results and complications in 222 consecutive procedures.

PURPOSE: To evaluate technical outcome and safety of computed tomographic (CT) fluoroscopy-guided percutaneous fiducial marker placement before CyberKnife stereotactic radiosurgery. MATERIALS AND METHODS: Retrospective analysis was performed of 196 patients (106 men) undergoing CT fluoroscopy-guided fiducial marker placement in 222 consecutive procedures under local anesthesia from March 2006 to February 2012. Technical success was defined as fiducial marker location in the tumor or vicinity suitable for CyberKnife radiosurgery evaluated on postinterventional planning CT. Complications were classified per Society of Interventional Radiology (SIR). RESULTS: One hundred ninety-six patients (age, 61.5 y ± 13.1) underwent percutaneous placement of 321 fiducial markers (mean per tumor, 1.2 ± 0.5; range, 1-4) in 37 primary tumors and 227 metastases in the thorax (n = 121), abdomen (n = 122), and bone (n = 21). Fiducial marker placement was technically successful in all procedures: intratumoral localization in 193 (60.1%), at tumor margin in 50 (15.6%), and outside of tumor in 78 cases (24.3%; mean distance to marker, 0.4 cm ± 0.6; range, 0-2.9 cm). Complications were observed in 63 placement procedures (28.4%), including minor self-limiting pneumothorax (n = 21; SIR class B) and self-limiting pulmonary hemorrhage (n = 35; SIR class A), and major pneumothorax requiring thoracostomy/drainage insertion (n = 14; SIR class D) and systemic toxicity of local anesthetic drug (n = 1; SIR class D). CONCLUSIONS: CT fluoroscopy-guided percutaneous fiducial marker placement can be performed with high technical success under local anesthesia in various anatomic regions. Although self-limiting in most cases, pneumothorax and pulmonary hemorrhage are frequently observed during fiducial marker implantation into lung tumors.

Validation of several SUV-based parameters derived from 18F-FDG PET for prediction of survival after SIRT of hepatic metastases from colorectal cancer.

UNLABELLED: (90)Y radioembolization (selective internal radiation therapy [SIRT]) is a valuable therapeutic option for unresectable hepatic metastases arising from primary colorectal cancer. The present study evaluated the prognostic value of (18)F-FDG PET/CT metabolic parameters for predicting survival after SIRT. METHODS: Eighty patients with hepatic metastases of colorectal cancer were treated with SIRT. (18)F-FDG PET/CT was performed at baseline and 3 mo after the treatment. Metabolic volume, total lesion glycolysis, and maximum and peak standardized uptake value (SUV(max) and SUV(peak), respectively) according to PET Response Criteria in Solid Tumors (PERCIST 1.0) were obtained from 3 liver lesions in each patient, and the corresponding percentage changes from baseline to follow-up were calculated. Tumor response was defined as more than a 30% decrease in these parameters. Furthermore, response was evaluated in accordance with Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Toxicity events and survival were recorded. RESULTS: Overall median survival after SIRT was 60 wk. Responders who had a change in metabolic volume or total lesion glycolysis had significantly longer survival (92 vs. 49 wk [P = 0.006] and 91 vs. 48 wk [P = 0.025], respectively). However, neither RECIST 1.1 criteria nor changes in SUV(peak) or SUV(max) after treatment predicted outcome (P = 0.086 for RECIST; P = 0.310 for change in SUV(peak); P = 0.155 for change in SUV(max)). CONCLUSION: Changes in metabolic volume and total lesion glycolytic rate as measured by (18)F-FDG PET predicted survival in patients with hepatic metastases from colorectal cancer, whereas changes in SUV(peak) or SUV(max) and RECIST 1.1 criteria did not predict survival.

Comparison of the survival and tolerability of radioembolization in elderly vs. younger patients with unresectable hepatocellular carcinoma.

BACKGROUND & AIMS: The European Network on Radioembolization with Yttrium-90 resin microspheres study group (ENRY) conducted a retrospective study to evaluate the outcomes among elderly (≥ 70 years) and younger patients (<70 years) with unresectable hepatocellular carcinoma (HCC) who received radioembolization at 8 European centers. METHODS: Patients with confirmed diagnosis of unresectable HCC who either progressed following resection or locoregional treatment and/or who were considered poor candidates for chemoembolization were evaluated by a multidisciplinary team for radioembolization with (90)Y-resin microspheres (SIR-Spheres; Sirtex Medical). The survival outcome and all adverse events were compared between the two age groups. RESULTS: Between 2003 and 2009, 128 elderly and 197 younger patients received radioembolization. Patients in both groups had similar demographic characteristics. Many elderly and younger patients alike had multinodular, BCLC stage C disease, invading both lobes (p = 0.648). Elderly patients had a lower tumor burden, a smaller median target liver volume (p = 0.016) and appeared more likely to receive segmental treatment (p = 0.054). Radioembolization was equally well tolerated in both cohorts and common procedure-related adverse events were predominantly grade 1-2 and of short duration. No significant differences in survival between the groups were found (p = 0.942) with similar median survival in patients with early, intermediate or advanced BCLC stage disease. CONCLUSIONS: Radioembolization appears to be as well-tolerated and effective for the elderly as it is for younger patients with unresectable HCC. Age alone should not be a discriminating factor for the management of HCC patients.

CT fluoroscopy-guided vertebral augmentation with a radiofrequency-induced, high-viscosity bone cement (StabiliT(®)): technical results and polymethylmethacrylate leakages in 25 patients.

OBJECTIVE: To assess the technical results of CT fluoroscopy-guided, radiofrequency-induced vertebral augmentation (StabiliT®) in terms of vertebral height restoration and polymethylmethacrylate (PMMA) leakages, occurring in 25 individual patients with vertebral compression fractures and osteolysis. MATERIALS AND METHODS: From 07/2010 to 08/2011, 25 patients (16 women, nine men; age 71 ± 14; range 41-89) with painful vertebral compression fractures due to osteoporosis (n = 19), metastases (n = 2) or multiple myeloma (n = 4) underwent vertebral augmentation with a radiofrequency-activated, high-viscosity polymethylmethacrylate (PMMA) bone cement (StabiliT® Vertebral Augmentation system; DFINE Europe GmbH, Mannheim) under local anesthesia. Thirty-four vertebrae (Th5-L5) were treated in 27 sessions under CT fluoroscopy guidance (128-row CT, Somatom Definition AS, Siemens, Erlangen) using a unilateral access and a cavity-creating osteotome prior to remote-controlled, hydraulically driven cement injection. 1/2/3 levels were treated in 21/5/1 session(s). Vertebral height change in the midsagittal plane (anterior, midvertebral, posterior endplate distance) and PMMA leaks were retrospectively evaluated using the postinterventional CT. RESULTS: All patients were successfully treated in the first session. Mean (MV ± SD) procedure time and amount of injected PMMA were 56 ± 14 min and 4.5 ± 1.4 ml, respectively. Mean anterior/midvertebral/posterior height gain was +7.1/+9.7/+0.4%. Small local vertebral leaks were observed in 18/34 vertebrae (53%) without any clinical sequelae. No major complications occurred. CONCLUSIONS: CT fluoroscopy-guided, RF-induced vertebral augmentation with a high-viscosity bone cement (StabiliT®) was safe and technically successful in all patients. Using a hydraulic cement injection technique, a moderate restoration of anterior and midvertebral height was seen while the system was not markedly superior to standard vertebroplasty regarding the frequency of minor asymptomatic PMMA leaks.

Immunogenic cell death biomarkers HMGB1, RAGE, and DNAse indicate response to radioembolization therapy and prognosis in colorectal cancer patients.

Radioembolization therapy (RE) is an efficient locoregional treatment for liver metastases from colorectal cancer. Serum biomarkers involved in immunogenic cell death are potentially valuable for early predicting therapy response and estimating prognosis. In a prospective observation study, blood samples were taken from 49 consecutive colorectal cancer patients with extensive hepatic metastases before, 24 and 48 hr after RE. Serum levels of high mobility group box 1 (HMGB1), receptor of glycation end products (RAGE) and activity of desoxyribonuclease were compared with response to therapy regularly determined radiologically 3 months after therapy and with overall survival. Serum levels of HMGB1 were increased already 24 hr after RE, while RAGE levels were decreased and DNAse remained unchanged. In radiological staging, 35 patients demonstrated disease progression while 14 patients had stable disease or remission. Serum HMGB1 levels 24 hr after RE were significantly higher in progressive than in nonprogressive patients while for RAGE and DNAse no difference was observed between the response groups. Concerning overall survival, high pretherapeutic (0 hr) and 24 hr levels of HMGB1 were associated with poor outcome. Multivariate analysis including HMGB1, tumor, liver and inflammation markers revealed HMGB1 and CRP as independent prognostic parameters. HMGB1 is a valuable serum biomarker for early estimation of therapy response and prognosis in colorectal cancer patients with liver metastases undergoing RE therapy.

CT fluoroscopy-guided percutaneous vertebroplasty in spinal malignancy: technical results, PMMA leakages, and complications in 202 patients.

OBJECTIVE: To retrospectively evaluate the incidence and clinical impact of local polymethylmethacrylate (PMMA) leaks and pulmonary cement embolisms occurring under CT fluoroscopy-guided vertebroplasty of symptomatic malignant vertebral osteolyses. MATERIALS AND METHODS: From December 2001 to June 2009, 202 cancer patients (116 women, 86 men; age 63.2±8.6 years) with painful malignant vertebral osteolyses underwent vertebroplasty, with or without vertebral compression fracture. A total of 331 vertebrae were treated in 231 sessions under CT fluoroscopy guidance (120 kV; 10­25 mA; single slice, 4-, 16-, and 128-row CT). In the pre-vertebroplasty CT, the following items were assessed: osteolytic destruction (0, ≤25, ≤50, ≤75, or ≤100%) of vertebral cross-sectional area, posterior wall, and circumference; presence of perivertebral and degree of epidural (no, mild, moderate) soft tissue involvement. Local PMMA leaks were analyzed using the post-vertebroplasty CT. Pulmonary cement embolisms were evaluated in all patients having undergone radiography (CR; n053) or CT (n088) of the chest after vertebroplasty due to their underlying disease. Patient charts were reviewed regarding adverse events. RESULTS: Of 331 treated vertebrae, 32, 20.2, and 15.7% showed more than 50% osteolytic involvement of the vertebral cross-sectional area, posterior wall, and circumference, respectively. Mild or moderate epidural involvement was seen in 13.0 and 8.4%. Local PMMA leakage rate was 58.6% (194 of 331 vertebrae). Pulmonary cement embolisms (segmental, n010; central, n01) were seen after 7.8% of the procedures with follow-up imaging of the chest. No major complications occurred within a 30-day period after vertebroplasty. CONCLUSION: Vertebroplasty of spinal malignancy can be safely performed under CT fluoroscopy guidance even in patients with substantial osteolytic involvement. In our patient collective, PMMA leaks and pulmonary cement embolisms visualized in post-procedural radiography and CT images had no clinical impact.

Predictive and prognostic value of circulating nucleosomes and serum biomarkers in patients with metastasized colorectal cancer undergoing Selective Internal Radiation Therapy.

BACKGROUND: Selective Internal Radiation Therapy (SIRT) is a new and effective locoregional anticancer therapy for colorectal cancer patients with liver metastases. Markers for prediction of therapy response and prognosis are needed for the individual management of those patients undergoing SIRT. METHODS: Blood samples were prospectively and consecutively taken from 49 colorectal cancer patients with extensive hepatic metastases before, three, six, 24 and 48 h after SIRT to analyze the concentrations of nucleosomes and further laboratory parameters, and to compare them with the response to therapy regularly determined 3 months after therapy and with overall survival. RESULTS: Circulating nucleosomes, cytokeratin-19 fragments (CYFRA 21-1), carcinoembryonic antigen (CEA), C-reactive protein (CRP) and various liver markers increased already 24 h after SIRT. Pretherapeutical levels of CYFRA 21-1, CEA, cancer antigen 19-9 (CA 19-9), asparate-aminotransferase (AST) and lactate dehydrogenase (LDH) as well as 24 h values of nucleosomes were significantly higher in patients suffering from disease progression (N = 35) than in non-progressive patients (N = 14). Concerning overall survival, CEA, CA 19-9, CYFRA 21-1, CRP, LDH, AST, choline esterase (CHE), gamma-glutamyl-transferase, alkaline phosphatase, and amylase (all 0 h, 24 h) and nucleosomes (24 h) were found to be prognostic relevant markers in univariate analyses. In multivariate Cox-Regression analysis, the best prognostic model was obtained for the combination of CRP and AST. When 24 h values were additionally included, nucleosomes (24 h) further improved the existing model. CONCLUSION: Panels of biochemical markers are helpful to stratify pretherapeutically colorectal cancer patients for SIR-therapy and to early estimate the response to SIR-therapy.

Transarterial hepatic yttrium-90 radioembolization in patients with unresectable intrahepatic cholangiocarcinoma: factors associated with prolonged survival.

INTRODUCTION: In unresectable intrahepatic cholangiocarcinoma (ICC), systemic chemotherapy often is viewed as the only option, although efficacy is limited. Radioembolization (RE) using yttrium-90 ((90)Y) microspheres is an accepted therapy for patients with hepatocellular-carcinoma or metastatic liver tumors. However, there are limited data on the value of RE in patients with ICC and few data on factors influencing prognosis. The purpose of our retrospective analysis was to establish which factors influenced time-to-progression (TTP) and overall survival (OS). METHODS: Patients with unresectable ICC were treated with (90)Y resin-microspheres and assessed at 3-monthly intervals. Radiologic response was evaluated by using Response Criteria in Solid Tumors (RECIST). Baseline characteristics, biochemical/clinical toxicities, and response were examined for impact on TTP and OS. RESULTS: Thirty-four treatments were administered to 33 patients without major complications. By RECIST, 12 patients had a partial response, 17 had stable disease, and 5 had progressive disease after 3 months. The median OS was 22 months posttreatment and 43.7 months postdiagnosis. Median TTP was 9.8 months. Survival and TTP were significantly prolonged in patients with ECOG 0 (vs. ECOG 1 or 2; median OS: 29.4, 10, and 5.1 months; TTP: 17.5, 6.9, and 2.4 months), tumor burden ≤25% (OS: 26.7 vs. 6 months; TTP: 17.5 vs. 2.3 months), or tumor response (PR or SD vs. PD; OS: 35.5, 17.7 vs. 5.7 months; TTP: 31.9, 9.8 vs. 2.5 months), respectively (P < 0.001). CONCLUSIONS: Radioembolization is an effective and safe option for patients with unresectable ICC. Predictors for prolonged survival are performance status, tumor burden, and RECIST response.

Radioembolization of symptomatic, unresectable neuroendocrine hepatic metastases using yttrium-90 microspheres.

PURPOSE: To evaluate safety, efficacy, and symptom-control of radioembolization in patients with unresectable liver metastases from neuroendocrine tumors (NETLMs). MATERIALS AND METHODS: Forty-two patients (mean age of 62 years) with treatment-refractory NETLMs underwent radioembolization using yttrium-90 ((90)Y) resin microspheres. Posttreatment tumor response was assessed by cross-sectional imaging using the Response Evaluation Criteria in Solid Tumors (RECIST) and tumor-marker levels. Laboratory and clinical toxicities and clinical symptoms were monitored. RESULTS: The median activity delivered was 1.63 GBq (range 0.63-2.36). Imaging follow-up using RECIST at 3-month follow-up demonstrated partial response, stable disease, and progressive disease in 22.5, 75.0, and 2.5% of patients, respectively. In 97.5% of patients, the liver lesions appeared hypovascular or partially necrotic. The mean follow-up was 16.2 months with 40 patients (95.2%) remaining alive. The median decrease in tumor-marker levels at 3 months was 54.8% (chromogranin A) and 37.3% (serotonin), respectively. There were no acute or delayed toxicities greater than grade 2 according to Common Terminology Criteria for Adverse Events [CTCAE (v3.0)]. No radiation-induced liver disease was noted. Improvement of clinical symptoms 3 months after treatment was observed in 36 of 38 symptomatic patients. CONCLUSION: Radioembolization with (90)Y-microspheres is a safe and effective treatment option in patients with otherwise treatment-refractory NETLMs. Antitumoral effect is supported by good local tumor control, decreased tumor-marker levels, and improved clinical symptoms. Further investigation is warranted to define the role of radioembolization in the treatment paradigm for NETLMs.