Robust evidence for long-term survival with 90Y radioembolization in chemorefractory liver-predominant metastatic colorectal cancer.

OBJECTIVES: Our aim was to provide further evidence for the efficacy/safety of radioembolization using yttrium-90-resin microspheres for unresectable chemorefractory liver metastases from colorectal cancer (mCRC). METHODS: We followed 104 consecutively treated patients until death. Overall survival (OS) was calculated from the day of the first radioembolization procedure. Response was defined by changes in tumour volume as defined by Response Evaluation Criteria in Solid Tumours (RECIST) v1.0 and/or a ≥30 % reduction in serum carcinoembryonic antigen (CEA) at 3 months. RESULTS: Survival varied between 23 months in patients who had a complete response to prior chemotherapy and 13 months in patients with a partial response or stable disease. Median OS also significantly improved (from 5.8 months to 17.1 months) if response durability to radioembolization extended beyond 6 months. Patients with a positive trend in CEA serum levels (≥30 % reduction) at 3 months post-radioembolization also had a survival advantage compared with those who did not: 15.0 vs 6.7 months. Radioembolization was well tolerated. Grade 3 increases in bilirubin were reported in 5.0 % of patients at 3 months postprocedure. CONCLUSIONS: After multiple chemotherapies, many patients still have a good performance status and are eligible for radioembolization. This single procedure can achieve meaningful survivals and is generally well tolerated. KEY POINTS: • After multiple chemotherapies, many patients are still eligible for radioembolization (RE). • RE can achieve meaningful survival in patients with chemorefractory liver-predominant metastatic colorectal cancer (mCRC). • Tumour responsiveness to prior systemic treatments is a significant determinant of overall survival (OS) after RE. • Radioembolization in patients with a good performance status is generally well tolerated.

Safety of Radioembolization with (90)Yttrium Resin Microspheres Depending on Coiling or No-Coiling of Aberrant/High-Risk Vessels.

PURPOSE: To evaluate the safety of radioembolization (RE) with (90)Yttrium ((90)Y) resin microspheres depending on coiling or no-coiling of aberrant/high-risk vessels. MATERIALS AND METHODS: Early and late toxicity after 566 RE procedures were analyzed retrospectively in accordance with the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE v3.0). For optimal safety, aberrant vessels were either coil embolized (n = 240/566, coiling group) or a more peripheral position of the catheter tip was chosen to treat right or left liver lobes (n = 326/566, no-coiling group). RESULTS: Clinically relevant late toxicities (≥ Grade 3) were observed in 1% of our overall cohort. The no-coiling group had significantly less "any" (P = 0.0001) or "clinically relevant" (P = 0.0003) early toxicity. There was no significant difference (P > 0.05) in delayed toxicity in the coiling versus the no-coiling group. No RE-induced liver disease was noted after all 566 procedures. CONCLUSION: RE with (90)Y resin microspheres is a safe and effective treatment option. Performing RE without coil embolization of aberrant vessels prior to treatment could be an alternative for experienced centers.

[Stabilization of the pelvic ring with photodynamic bone stabilization (IlluminOss™)]. / Stabilisierung einer Beckeninsuffizienzfraktur mit einem photosensiblen Kunststoff (IlluminOss™).

We describe the case of an 88-year-old woman who presented with painful symptoms of the pelvis after low-energy trauma. Conservative treatment with pain therapy and pain-adapted mobilization was unsuccessful. Diagnostics showed a fragility fracture of the pelvic ring; therefore, we performed photodynamic bone stabilization (IlluminOss™) of the pubic bone and percutaneous cement-augmented fixation of the iliosacral joint assisted by computed tomography (CT) fluoroscopy. Imaging showed a stable healed fracture 4 months after surgery.

Radioembolization with Yttrium-90 microspheres (SIRT) in pancreatic cancer patients with liver metastases: efficacy, safety and prognostic factors.

OBJECTIVE: To analyze the clinical efficacy of (90)Y radioembolization in liver metastases from pancreatic cancer, to describe treatment toxicities and to identify biomarkers as predictors of outcome. METHODS: Data from 19 pancreatic cancer patients (9 females/10 males) who had received (90)Y radioembolization for metastatic liver disease between 06/2004 and 01/2011 were analyzed retrospectively. RESULTS: The median age at (90)Y radioembolization was 63 years (range 43-77). In 16 patients, previous palliative gemcitabine-based chemotherapy was given for metastatic disease. Objective response in the liver after (90)Y radioembolization was 47%. Median local progression-free survival in the liver was 3.4 months (range 0.9-45.0). Median overall survival (OS) was 9.0 months (range 0.9-53.0) and 1-year survival was 24%. Cox regression models for baseline biomarkers at (90)Y radioembolization revealed correlations of increased carbohydrate antigen 19-9 (p = 0.02) and C-reactive protein (p = 0.03) with shorter OS. Short-term adverse events (nausea, vomiting, fatigue, fever and abdominal pain) did not exceed grade 3. As long-term adverse events, liver abscesses, gastroduodenal ulceration, cholestasis and cholangitis, ascites and spleen infarction were observed. CONCLUSION: (90)Y radioembolization is able to induce an encouraging local response rate of liver metastases of pancreatic cancer patients. Most short-term toxicities are manageable; however, patients should be followed up carefully for severe long-term toxicities.

Multimodality treatment for early-stage hepatocellular carcinoma: a bridging therapy for liver transplantation.

PURPOSE: To evaluate the efficiency of a multimodality approach consisting of transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) as bridging therapy for patients with hepatocellular carcinoma (HCC) awaiting orthotopic liver transplantation (OLT) and to evaluate the histopathological response in explant specimens. MATERIALS AND METHODS: Between April 2001 and November 2011, 36 patients with 50 HCC nodules (1.4-5.0 cm, median 2.8 cm) on the waiting list for liver transplantation were treated by TACE and RFA. The drop-out rate during the follow-up period was recorded. The local efficacy was evaluated by histopathological examination of the explanted livers. RESULTS: During a median follow-up time of 29 (4.0-95.3) months the cumulative drop-out rate for the patients on the waiting list was 0, 2.8, 5.5, 11.0, 13.9 and 16.7% at 3, 6, 12, 24, 36 and 48 months, respectively. 16 patients (with 26 HCC lesions) out of 36 (44.4%) were transplanted by the end of study with a median waiting list time of 13.7 (2.5-37.8) months. The histopathological examination of the explanted specimens revealed a complete necrosis in 20 of 26 HCCs (76.9%), whereas 6 (23.1%) nodules showed viable residual tumor tissue. All transplanted patients are alive at a median time of 29.9 months. Imaging correlation showed 100% specificity and 66.7% sensitivity for the depiction of residual or recurrent tumor. CONCLUSION: We conclude that TACE combined with RFA could provide an effective treatment to decrease the drop-out rate from the OLT waiting list for HCC patients. Furthermore, this combination therapy results in high rates of complete tumor necrosis as evaluated in the histopathological analysis of the explanted livers. Further randomized trials are needed to demonstrate if there is a benefit in comparison with a single-treatment approach.

Practical vascular anatomy in the preparation of radioembolization.

As the incidence of primary and metastatic liver cancer continues to increase, the use of minimally invasive techniques as a treatment option is becoming more common. Radioembolization, a form of intra-arterial brachytherapy, is a technique where particles of glass or resin, impregnated with the isotope 90yttrium (90Y), are infused through a catheter directly into the hepatic arteries. This modality is based on the fact that hepatic malignancies receive their blood supply from the hepatic artery, whereas normal hepatocytes are perfused mostly from the portal circulation, which allows delivery of high doses to the tumor vasculature with relative sparing of normal liver tissue. This has been shown to be effective for both primary and metastatic tumors. A variety of complications may be related to hepatic intra-arterial treatments, especially to the gastroduodenal region. These complications are known to come from inadvertent extrahepatic infusion of 90Y particles, through arteries originating from the hepatic arterial branches such as the falciform artery, cystic artery, arteries from the pancreaticoduodenal arcade, gastroduodenal artery, or right gastric artery. Surgeons and interventional radiologists rely on accurate imaging and assessment of the hepatic arterial supply. It is important to know the common anatomic variations and technical considerations before radioembolization. We recommend an aggressive occlusion of all the above-mentioned arteries; further, clinicians should watch out for any other aberrant branches, and if in doubt, they ought to be coiled.

FDG-PET-CT and whole-body MRI for triage in patients planned for radioembolisation therapy.

PURPOSE: The purpose was to evaluate the potential of FDG-PET-CT and whole-body MRI (WB-MRI) as diagnostic triage methods for patients planned for radioembolisation of metastatic liver disease. MATERIALS AND METHODS: 135 patients with multifocal liver metastases were evaluated for potential palliative therapy with radioembolisation using 90-Yttrium microspheres. All patients were examined consecutively with FDG-PET-CT and WB-MRI for exclusion of relevant extra-hepatic tumor manifestations. All patients underwent 99mTc-albumine angiography followed by scintigraphy to exclude significant hepato-pulmonary shunting. RESULTS: Out of the 135 patients included into the pre-therapeutic diagnostic algorithm, 56% were eligible and received radioembolisation, while 44% could not be treated. In 91% the exclusion criteria was diagnosis of significant extra-hepatic metastatic disease. In 85% exclusion diagnosis was made concordantly by both FDG-PET-CT and WB-MRI, in 9% diagnosis was provided by PET-CT, in 6% by WB-MRI alone. Patient-based sensitivity for detection of extra-hepatic disease was 94% for PET-CT and 91% for WB-MRI. False-positive diagnosis of extrahepatic disease leading to exclusion for radioembolisation therapy was made in 2% of patients, in one patient by PET-CT and in one patient by WB-MRI alone. Overall, specificity for inclusion of radioembolisation therapy by combining both modalities was 99%. In 9% of patients angiographic diagnosis made radioembolisation impossible, in 7% solely the angiographic findings were decisive. CONCLUSION: Both FDG-PET-CT and WB-MRI are efficient diagnostic triage methods for patients planned for radioembolisation of liver metastases. Overall, FDG-PET-CT shows a trend to higher diagnostic accuracy compared to WB-MRI and may be used as imaging method of choice as a standalone examination. In combination, both modalities exhibited high sensitivity for the diagnosis of extra-hepatic tumor manifestations and result in high specificity.

Multimodality treatment with conventional transcatheter arterial chemoembolization and radiofrequency ablation for unresectable hepatocellular carcinoma.

BACKGROUND/AIMS: To evaluate the efficacy of multimodality treatment consisting of conventional transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) in patients with non-resectable and non-ablatable hepatocellular carcinoma (HCC). METHODS: In this retrospective study, 85 consecutive patients with HCC (59 solitary, 29 multifocal HCC) received TACE followed by RFA between 2001 and 2010. The mean number of tumors per patient was 1.6 ± 0.7 with a mean size of 3.0 ± 0.9 cm. Both local efficacy and patient survival were evaluated. RESULTS: Of 120 treated HCCs, 99 (82.5%) showed a complete response (CR), while in 21 HCCs (17.5%) a partial response was depicted. Patients with solitary HCC revealed CR in 91% (51/56); in patients with multifocal HCC (n = 29) CR was achieved in 75% (48 of 64 HCCs). The median survival for all patients was 25.5 months. The 1-, 2-, 3- and 5-year survival rates were 84.6, 58.7, 37.6 and 14.6%, respectively. Statistical analysis revealed a significant difference in survival between Barcelona Clinic Liver Cancer (BCLC) A (73.4 months) and B (50.3 months) patients, while analyses failed to show a difference for Child-Pugh score, Cancer of Liver Italian Program (CLIP) score and tumor distribution pattern. CONCLUSION: TACE combined with RFA provides an effective treatment approach with high local tumor control rates and promising survival data, especially for BCLC A patients. Randomized trials are needed to compare this multimodality approach with a single modality approach for early-stage HCC.

Changes in normal liver and spleen volume after radioembolization with (90)Y-resin microspheres in metastatic breast cancer patients: findings and clinical significance.

PURPOSE: In clinical trials with yttrium-90-resin-microspheres for the management of colorectal cancer liver metastases, it was observed that radioembolization might result in splenomegaly and an increase in portal vein size. Subclinical hepatitis in normal liver tissue as well as the effects of radioembolization and prior chemotherapy are suspected to be responsible for this phenomenon. The purpose of this study was to quantify the changes in liver and spleen volume and portal vein diameter after radioembolization. METHODS: Twenty-seven patients with liver-dominant metastatic disease from breast cancer who had not responded to chemotherapy or had to abandon chemotherapy because of its toxic effects were evaluated. Changes in liver and spleen volume and portal vein diameter as well as liver tumor volume and diameter were quantified using computed tomography scans. RESULTS: Radioembolization was associated with a significant mean decrease in the whole liver volume of 10.2% (median 16.7%; P = 0.0024), mainly caused by a reduction in the right lobe volume (mean 16.0%; P < 0.0001). These changes were accompanied by a significant increase in the diameter of the main portal vein (mean 6.8%; P < 0.0001) as well as splenic volume (mean 50.4%; P < 0.0001). Liver-tumor volume and diameter decreased by a median of 24 and 39.7%. CONCLUSIONS: Radioembolization is an effective treatment for tumor size reduction in patients with breast cancer liver metastases. Treatment is associated with changes of hepatic parenchymal volume, splenic volume, and portal vein size that appear not to represent clinically important sequelae in this patient cohort.

Arterial therapies of non-colorectal cancer metastases to the liver (from chemoembolization to radioembolization).

Treatment of primary and secondary hepatic malignancies with transarterial chemoembolization (TACE) represents an essential component of interventional oncology known for many years and performed by many interventional radiologists first in primary liver tumors and nowadays even in metastases of different origins. Radioembolization (RE) has been introduced to the clinical arsenal of cytoreductive modalities in recent years. There is growing evidence for efficiency in liver tumors of various entities, with the most prominent ones being hepatocellular carcinoma, colorectal cancer, and neuroendocrine tumors. Hepatic metastases of other tumor entities (breast cancer, malignant melanoma, and pancreatic cancer) are treatment-sensitive. This article focuses on procedural and technical aspects for selection, preparation, and performance of treatment as well as the results in metastatic breast cancer, neuroendocrine tumors, melanoma, and pancreatic cancer giving an overview of the results after RE, transarterial embolization, or TACE.

[Diagnosis and multimodal therapy for hepatocellular carcinoma]. / Diagnose und multimodale Therapie des hepatozellulären Karzinoms.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death in the world. The majority of HCCs develops on the basis of a chronic liver disease. This often complicates diagnosis and therapy. Non-invasive diagnostic criteria are based on dynamic imaging techniques and the serum level of AFP (alpha-fetoprotein). When evaluating HCC patients for therapy, besides tumor burden and localisation, the therapeutic evaluation must also consider the general condition of the patient and his/her liver function. For this purpose, the BCLC algorithm of the Barcelona Clinic for Liver Disease has proven helpful. Only one-third of the patients can be cured by resection, transplantation or local tumour ablation. In locally advanced cases transarterial procedures including transarterial chemoembolisation and radioembolisation are applied. HCC is a chemo-resistant tumour and chemotherapy is not accepted as standard of care in HCC. Sorafenib is the first systemic treatment with proven efficacy approved for the treatment of advanced and metastatic HCC. Interdisciplinary management of HCC patients is essential in order to provide every patient with the optimal therapy at his specific stage of disease.

Radiofrequency ablation after selective internal radiation therapy with Yttrium90 microspheres in metastatic liver disease-Is it feasible?

This retrospective study analyzes, whether patients suffering from extensive hepatic metastatic disease treated with SIRT can become suitable candidates for RFA.Within 38 months 46 patients (26 female, 20 male; age 32-75 years) bearing an extensive hepatic metastatic disease were treated with SIRT. Patients suffered from metastases of breast cancer (16/46), colorectal cancer (CRC) (21/46), neuroendocrine (3/46), and other primary carcinomas (6/46). The indication for SIRT was otherwise untreatable metastases confined to the liver. Forty-three patients received single-session whole-liver radioembolization treatment using Yttrium90 resin microspheres with a mean activity of 2.13GBq. In 1 patient SIRT was confined to the left and in 2 patients to the right liver lobe. In 3 patients major complications (2/3 gastric ulceration and 1/3 oedematous pancreatitis) and in 24 patients minor complications occurred (acute abdominal/epigastric pain and/or nausea). Follow-up CT and/or MRI were obtained in 44 of 46 patients. In 5 of 44 patients tumor load decreased substantially (3/5 breast cancer, 1/5 CRC and 1/5 pancreatic cancer) making RFA feasible. The patients were referred for RFA after the first 3-month follow-up. RFA of the liver was successful in all cases in terms of complete ablation. In selected patients radioembolization is able to downstage liver metastases to an extent making a subsequent RFA suitable and therefore allows increasing the number of patients with a "complete response" after a minimally invasive therapy.

[Therapy response of liver tumors after selective internal radiation therapy]. / Therapieresponse von Lebertumoren nach selektiver interner Radiotherapie.

Selective internal radiation therapy (SIRT) is used for the treatment of patients with liver tumors, especially for those with hepatocellular carcinoma (HCC) or liver metastases from various primary tumors. Currently this innovative treatment concept is recommended when established state-of-the-art treatment regimes have failed and tumor progression is noted or if the treatment has to be abandoned because of intolerable toxic effects. For SIRT small biocompatible microspheres (SIR-Spheres(R)) are labelled with the radioactive isotope 90Yttrium, a pure beta emitter, and are superselectively infused into the hepatic arteries. The microspheres are collected in the precapillary vessels in and surrounding the tumor. The beta radiation of 90Yttrium has an average penetration in tissue of approximately 2.5 mm and results in very high doses of radiation being selectively targeted to metastases providing protection to the surrounding healthy liver tissue. In this paper we review the results of SIRT in patients with hepatic metastases from colorectal cancer, breast cancer, neuroendocrine tumors and primary liver cancer (HCC).

Fibrosis, portal hypertension, and hepatic volume changes induced by intra-arterial radiotherapy with 90yttrium microspheres.

PURPOSE: To identify changes in hepatic parenchymal volume, fibrosis, and induction of portal hypertension following radioembolization with glass microspheres for patients with metastatic disease to the liver. RESULTS: In our series of sequential bilobar (n = 17) treatments, a mean decrease in liver volume of 11.8% was noted. In this group, a mean splenic volume increase of 27.9% and portal vein diameter increase of 4.8% were noted. For patients receiving unilobar treatments (n = 15), mean ipsilateral lobar volume decrease of 8.9%, contralateral lobar hypertrophy of 21.2%, and a 5.4% increase in portal vein diameter were also noted. These findings were not associated with clinical toxicities. CONCLUSION: (90)Yttrium radioembolization utilizing glass microspheres in patients with liver metastases results in changes of hepatic parenchymal volume and also induced findings suggestive of fibrosis and portal hypertension. Further studies assessing the long-term effects are warranted.

[Update on chemoinfusion and chemoembolization treatments]. / Update Chemoperfusion und -embolisation.

In the last two decades image-guided interventional catheterizations and percutaneous ablative regional treatment procedures have revolutionized the therapy of nonresectable primary and secondary liver tumours. A distinction is made between chemoablative procedures and thermo- and radioablative procedures. The main chemoablative interventions are transarterial infusion chemotherapy (HAIC; hepatic arterial infusion chemotherapy) and transarterial (chemo-)embolization (TACE/TAE). The object of the transarterial treatment procedures is to deliver the highest possible concentration of a chemotherapy agent or combination of chemotherapy agents directly into the tumour by way of the blood vessels supplying it, while at the same time keeping the systemic effects of the drugs as small as possible. Transarterial chemoperfusion to the liver can be applied in the treatment of all primary and secondary hepatic tumours, but the main indications are hepatocellular carcinoma (HCC) and metastases from colorectal primary tumours.

[Developments and perspectives in radioablative techniques]. / Entwicklungen und Perspektiven radioablativer Verfahren.

The encouraging preliminary results of radioembolization therapy in hepatocellular carcinoma and liver metastases from colorectal cancer have suggested that this mode of therapy could also be successful in breast and neuroendocrine metastases from colorectal cancer. (90)Yttrium microspheres in combination with radiosensitizing agents and growth factor inhibitors present opportunities to evaluate its application in combinatorial treatment paradigms with modern chemotherapy regimens. Other randomized trials are needed in hepatocellular carcinoma, to compare radioembolization with (90)yttrium against transarterial chemoembolization, bland embolization, drug-eluting beads, and best supportive care. A further potential research area besides the application of radioembolization for extrahepatic tumors is the determination of quality of life in randomized studies comparing radioembolization with systemic chemotherapy regimens with or without percutaneous radiation therapies.

[Interventional oncology for lung tumors]. / Interventionelle Onkologie bei Lungentumoren.

Lung tumors and pulmonary metastases together are the most common cause of cancer-related death in men and the second most frequent in women. Up to now, surgical resection has remained the gold standard in the treatment of pulmonary tumors, being the only treatment option that was potentially curative and offered the possibility of a significant increase in life expectancy after successful therapy. Over the past decade, percutaneous radiofrequency ablation (RFA) has gained worldwide acceptance in the treatment of primary and secondary tumors of the liver with curative intent, so that indications for RFA have been extended to embrace tumors in other organs, e.g. the lung. Since the first case results were described, the number of publications dealing with the treatment of lung tumors using thermal ablative therapies has increased significantly. The aims of the present article are to give a short overview of emerging therapies such as cyberknife surgery and also, especially, to describe the indications for and technique of RFA, to discuss the ideal method of follow-up, and to highlight possible complications of the therapy and the current results of RFA of primary and secondary lung tumors. In addition, the value of combining RFA with other therapy modes (especially chemotherapy and radiation therapy)is briefly treated.

Vertebroplasty in the treatment of osteoporotic vertebral body fracture.

During the last few years, vertebroplasty has gained a wide acceptance for the treatment of painful osteoporotic vertebral body fractures and osteolytic changes. However, new guidelines with significant changes in indications and technique were published recently in Europe. Therefore, the aim of this review is to highlight recent changes in indications for vertebroplasty, patient work-up and changes in procedural technique, and to give an overview of patient outcome and possible complications. Therefore, technical details like different types of fluoroscopy, needle placement, pain management during the intervention, recommended equipment, including bone cement, and the use of venography are discussed. Postprocedural issues are noted, including the risk of minor and major complications and the expected outcome of the treated patients.

Percutaneous vertebroplasty in tumoral osteolysis.

Percutaneous vertebroplasty is a minimally invasive, radiologically guided procedure in which bone cement is injected into structurally weakened or destructed vertebrae in order to achieve additional biomechanical stability. In addition to treating osteoporotic vertebral fractures, this technique gains popularity to relieve pain by stabilizing vertebrae compromised by, for example, metastases, aggressive hemangiomas or multiple myeloma that are at risk of pathologic fracture. Since conservative treatment with narcotic analgesics, bed rest, biphosphonates and back bracing for several weeks is often ineffective and the analgesic effect of radiation therapy is delayed, percutaneous vertebroplasty may play a beneficial role in the management of metastases to the spine.