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ZusammenfassungAmbulante PET/CT-Leistungen sind für gesetzlich Versicherte nur für eine begrenzte Anzahl an Indikationen über den EBM erstattungsfähig. Für andere wichtige Indikationen erweist sich der Prozess der Beurteilung und Aufnahme in den EBM als außerordentlich langwierig, sodass über die Einzelfallentscheidung hinaus Sonderwege etabliert wurden, durch die sich Betroffene einer PET/CT-Untersuchung zulasten der GKV unterziehen können. Hierzu gehören die Besondere Versorgung, die ASV und Erprobungsstudien. Zusätzlich zur komplexen Erstattungssituation hat der Gesetzgeber den PET-Anwendern Qualitätssicherungsmaßnahmen auferlegt, deren Nichteinhaltung Sanktionen nach sich zieht. Dieser Artikel soll einen Überblick über die Möglichkeiten, Anforderungen und Hürden bieten, ambulante PET-Diagnostik über die GKV abzurechnen.

Background Insulinomas are rare insulin-producing pancreatic neuroendocrine tumours leading to severe episodes of hypoglycaemia. Surgery is the predominant curative therapy. Methods We report here the first paediatric case of an insulinoma of the pancreatic body resected completely robotically under ultrasound guidance in a 10-year-old male with multiple endocrine neoplasia type 1. The port set-up was adapted for the narrowed dimensions of the paediatric peritoneal space. We comment on technical key steps for the organ-preserving procedure that was performed in close proximity to critical anatomic structures, with supporting video. Preoperative diagnostics, including endoscopic ultrasound, to determine surgical management are highlighted. Results Following an uneventful post-operative course, the boy was discharged on day 11 with normalised glucose-metabolism. A pseudocyst developing after 4 weeks was treated with endoscopic stenting. Conclusions The applicability of a robotic surgical system in limited space conditions such as found in the paediatric abdominal cavity is demonstrated here for pancreatic surgery.

Purpose Interstitial high-dose-rate brachytherapy (BT) is an alternative treatment option to stereotactic body radiotherapy (SBRT) for the ablative treatment of liver malignancies. The aim of the present comparative planning study was to reveal the possibilities and limitations of both techniques with regard to dosimetric properties. Methods and Materials Eighty-five consecutive patients with liver malignancy diagnosis were treated with interstitial BT between 12/2008 and 09/2009. The prescription dose of BT varied between 15 and 20 Gy, depending on histology. For dosimetric comparison, virtual SBRT treatment plans were generated using the original BT planning CTs. Additional margins reflecting the respiratory tumor motion were added to the target volumes for SBRT planning. Results The mean PTVBT was 34.7 cm3 (0.5–410.0 cm3) vs. a mean PTVSBRT of 73.2 cm3 (6.1–593.4 cm3). Regarding the minimum peripheral dose (D99.9), BT achieved the targeted prescription dose of 15 Gy/20 Gy better without violating organ at risk constraints. The dose exposure of the liver was significantly influenced by treatment modality. The liver exposure to 5 Gy was statistically lower with 611 ± 43 cm3 for BT as compared with 694 ± 37 cm3 for SBRT plans (20-Gy group, p = 0.001), corresponding to 41.8% vs. 45.9% liver volume, respectively. Conclusions To the best of our knowledge, this is the first report on the comparison of clinically treated liver BT treatments with virtually planned SBRT treatments. The planning study showed a superior outcome of BT regarding dose coverage of the target volume and exposed liver volume. Nevertheless, further studies are needed to determine ideal applicability for each treatment approach.

In this pilot trial, we investigate the safety of CT-guided high-dose-rate brachytherapy (HDR-BT) as a local ablative treatment for renal masses not eligible for resection or nephrectomy. We investigated renal function after irradiation by HDR-BT in 16 patients (11 male, 5 female, mean age 76 years) with 20 renal lesions (renal cell carcinoma n = 18; renal metastases n = 2). Two patients had previous contralateral nephrectomy and two had ipsilateral partial nephrectomy. Six lesions had a hilar localization with proximity to the renal pelvis and would have not been favorable for thermal ablation. Renal function loss was determined within 1 year after HDR-BT by renal scintigraphy and laboratory parameters. Further investigations included CT and MRI every 3 months to observe procedural safety and local tumor control. Renal function tests were analyzed by Wilcoxon’s signed rank test with Bonferroni–Holm correction of p-values. Survival and local tumor control underwent a Kaplan–Meier estimation. Median follow-up was 22.5 months. One patient required permanent hemodialysis 32 months after repeated HDR-BT and contralateral radiofrequency ablation of multifocal renal cell carcinoma. No other patient developed a significant worsening in global renal function and no gastrointestinal or urogenital side effects were observed. Only one patient died of renal tumor progression. Local control rate was 95% including repeated HDR-BT of two recurrences. HDR-BT is a feasible and safe technique for the local ablation of renal masses. A phase II study is recruiting to evaluate the efficacy of this novel local ablative treatment in a larger study population.

Purpose Evaluation of efficacy and safety of CT- or MRI-guided high-dose-rate interstitial brachytherapy (iBT) in the treatment of advanced, imatinib refractory, metastatic gastrointestinal stroma tumors (GISTs) was the objective of this retrospective study. Methods and Materials A cumulative number of 40 unresectable metastases (30 hepatic, 10 peritoneal) were treated with iBT in 10 selected patients with histologically proven GISTs. Six patients had peritoneal disease, and 5 patients were even progressing under sunitinib (second line)—thus iBT was applied as a salvage maneuver. IBT uses an interstitially introduced 192iridium source in a high-dose-rate irradiation regime to destroy vital cells in a single fraction. Response to treatment was assessed clinically and with acquisition of MRI/CT every 3 months. Results Local tumor control was reached in 97.5% of all treated metastases during a median time of 25 months—only one local relapse was observed during followup. The median diameter of the irradiated lesions was 2.4 cm (range 0.6–11.2 cm); a median dose of 15 Gy (range 6.7–21.96 Gy) was applied. The median progression-free survival after iBT was 6.8 (range 3.0–20.2) months; the median overall survival was 37.3 months (range 11.4–89.7). Two major complications (Common Terminology for Adverse Events grade 3) occurred following the intervention: local hemorrhage and pneumothorax, successfully dealt with by angiographic embolization and pleural drainage, respectively. Conclusions In selected patients with metastatic, imatinib refractory GISTs, iBT safely enables high rates of local tumor control and presents an alternative, anti-neoplastic treatment option even in a salvage situation.

Numerous pilot studies and randomized comparisons have shown that interstitial brachytherapy (iBT) is capable of achieving high to very high rates of tumor control, for various tumor entities. These rates vary up to >90% after 12 months, even for large or very large tumors. A dose-dependence was demonstrated, and hepatic metastases of most tumor entities, including primary liver tumors, could be brought excellently under control with a 15–20 Gy radiation dose. In a randomized study, superiority of iBT compared with transarterial chemoembolization was shown, with a significantly longer time to progression and time to untreatable progression.

The brachytherapy catheter is usually implanted by the Seldinger method, as a rule under guidance by CT fluoroscopy. This demands a high degree of cooperation between interventional radiology and radiation therapy, in order to ensure optimum irradiation. For safety reasons, the usual setting is an in-patient one.

Worldwide, the incidence of cancer disease increased by 33% between 2005 and 2015. Progress in drug-based tumor therapy in recent years has continued to raise the importance of systemic treatment for a range of tumor entities at the metastatic stage. Nevertheless, metastasis-directed local tumor therapy has been demonstrated to be effective in several studies. In recent years, observation of long-term survival after local treatments has led to the establishment of the concept of oligometastatic disease. Limited metastatic spread may offer potential for curative outcomes after local therapies or surgery. The possibilities offered by modern radiological techniques have led to the development of minimally invasive therapies, such as radio-frequency ablation (RFA), which today is the most widely used of these and is supported by strongest evidence. Multimodal therapy directed at metastases is curatively successful with many patients, and when unsuccessful it is today achieving an increasingly long duration of palliation, which means that the cohort size needed to demonstrate an advantage in OS is becoming unrealistically large. Therefore, there is a need to define new endpoints for the stratification and assessment of initial response to therapy. These can act as surrogate markers for “depth of response.” They could include, for example, the quantification of biomarkers, such as circulating tumor DNA, obtained by liquid biopsy.

The aim of this single-center, open-label phase II study was to assess the efficacy of image-guided high-dose-rate (HDR) brachytherapy (iBT) compared with conventional transarterial embolization (cTACE) in unresectable hepatocellular carcinoma. Seventy-seven patients were treated after randomization to iBT or cTACE, as single or repeated interventions. Crossover was allowed if clinically indicated. The primary endpoint was time to untreatable progression (TTUP). Eligibility criteria included a Child–Pugh score of ≤ 8 points, absence of portal vein thrombosis (PVT) at the affected liver lobe, and ≤ 4 lesions. Survival was analyzed by using the Cox proportional hazard model with stratification for Barcelona Clinic Liver Cancer (BCLC) stages. Twenty patients were classified as BCLC-A (iBT/cTACE 8/12), 35 as BCLC-B (16/19), and 22 as BCLC-C (13/9). The 1-, 2-, and 3-year TTUP probabilities for iBT compared with cTACE were 67.5% versus 55.2%, 56.0% versus 27.4%, and 29.5% versus 11.0%, respectively, with an adjusted hazard ratio (HR) of 0.49 (95% confidence interval 0.27–0.89; p = 0.019). The 1-, 2-, and 3-year TTPs for iBT versus cTACE were 56.0% versus 28.2%, 23.9% versus 6.3%, and 15.9% versus 6.3%, respectively, with an adjusted HR of 0.49 (0.29–0.85; p = 0.011). The 1-, 2-, and 3-year OS rates were 78.4% versus 67.7%, 62.0% versus 47.3%, and 36.7% versus 27.0%, respectively, with an adjusted HR of 0.62 (0.33–1.16; p = 0.136). This explorative phase II trial showed a superior outcome of iBT compared with cTACE in hepatocellular carcinoma and supports proceeding to a phase III trial.

// Tina Streitparth 1 , Denis Schumacher 2 , Robert Damm 3 , Bjoern Friebe 3 , Konrad Mohnike 4 , Ortrud Kosiek 3 , Maciej Pech 3 , Jens Ricke 1 and Florian Streitparth 1 1 Department of Radiology, University Hospital Munich, Munich, Germany 2 Department of Neurology, Clinic of Magdeburg, Magdeburg, Germany 3 Department of Radiology, Otto-von-Guericke University Clinic Magdeburg, Magdeburg, Germany 4 DTZ, Berlin, Germany Correspondence to: Tina Streitparth, email: tina.streitparth@med.uni-muenchen.de Keywords: lung malignancies; radiofrequency ablation; colorectal cancer; microwave ablation Received: May 05, 2017 Accepted: November 11, 2017 Published: January 18, 2018 ABSTRACT Purpose: The purpose of this study was to evaluate the efficacy, safety and predictive factors of RFA of primary and secondary lung malignancies. Patients and Methods: 79 patients with 129 primary and secondary lung malignancies were enrolled in a retrospective study. We treated 74 pulmonary metastases of colorectal cancer, 13 malignant melanoma lesions, 13 renal cancer metastases, 5 primary lung malignancies and 24 tumors of other different entities. All patients were considered to be unsuitable candidates for surgery, radiotherapy or chemotherapy. The primary endpoint was local tumor control, secondary endpoints were overall survival, safety and predictive factors, e.g. distance to pleura, vessels and bronchi. Results: The median tumor size was 1.2 cm (0.5–3.0 cm). After a median follow-up of 14 months (3–81 months), the LTC was 85.3 %. There were 34 lesions (26.4%) with complete remission, 48 (37.2 %) partial remission, 28 (21.7%) stable disease and 19 lesions (14.7%) with progressive disease. We evaluated an OS of 27 months. Pneumothorax in 19 cases (14.7%) and pleural effusion in 2 cases (1.6 %) were the leading complications (CTCAE, 5 grade III adverse events). The only significant influence regarding the outcome after RFA was the initial tumor size ( p = 0.01). Distance to vessel, bronchi, and pleura showed no significant effect ( p = 0.81; p = 0.82; p = 0.80).

To evaluate the course of pro- and anti-inflammatory cytokines after 90Y-radioembolization (RE) of liver malignancies and to identify prognosticators for liver-related adverse events and survival. In 34 consecutive patients with secondary or primary liver tumors scheduled for RE, the following cytokines were measured prior to and 2 h, 3 days, and 6 weeks after RE: interleukin (IL) -1, IL-2, IL-4, IL-6, IL-8, tumor necrosis factor alpha (TNF-α), and interferon-γ. Liver function impairment was defined as an elevation of liver-related laboratory values as graded by CTCAE ≥ 2 and/or serum bilirubin ≥30 µmol/l and/or development of ascites at 6-week follow-up. Significant changes over time were seen in IL-1 (increase from 0.4 pg/ml (±0.7) at baseline to 1.1 pg/ml (±1.4) 3 days after RE (p = 0.02)), and in IL-6 (increase from 16.8 pg/ml (±21.8) at baseline to 54.6 pg/ml (±78.2) 3 days after RE (p = 0.003)). Baseline values of IL-6 and IL-8 were independently associated with liver function impairment at follow-up as well as decreased survival with an optimal cutoff at 6.53 and 60.8 pg/ml, respectively. Expected changes in pro- and anti-inflammatory cytokines after RE were shown. Furthermore, baseline values of IL-6 and IL-8 were associated with later liver dysfunction and survival. We hypothesize that these biomarkers are potential prognosticators and might help in patient selection for RE.

The objective of this study was to assess the influence of an iterative CT reconstruction algorithm (IA), newly available for CT-fluoroscopy (CTF), on image noise, readers’ confidence and effective dose compared to filtered back projection (FBP). Data from 165 patients (FBP/IA = 82/74) with CTF in the thorax, abdomen and pelvis were included. Noise was analysed in a large-diameter vessel. The impact of reconstruction and variables (e.g. X-ray tube current I) influencing noise and effective dose were analysed by ANOVA and a pairwise t-test with Bonferroni–Holm correction. Noise and readers’ confidence were evaluated by three readers. Noise was significantly influenced by reconstruction, I, body region and circumference (all p ≤ 0.0002). IA reduced the noise significantly compared to FBP (p = 0.02). The effect varied for body regions and circumferences (p ≤ 0.001). The effective dose was influenced by the reconstruction, body region, interventional procedure and I (all p ≤ 0.02). The inter-rater reliability for noise and readers’ confidence was good (W ≥ 0.75, p

Purpose: Needle track seeding in the local treatment of hepatocellular carcinoma (HCC) is not yet evaluated for catheter-based high-dose-rate brachytherapy (HDR-BT), a novel local ablative technique. Material and methods: We report a retrospective analysis of 100 patients treated on 233 HCC lesions by HDR-BT (using 588 catheters in total). No needle or catheter track irradiation was used. Minimum required follow-up with imaging was 6 months. In case of suspected needle track seeding (intra- and/or extrahepatic) in follow-up, image fusion of follow-up CT/MRI with 3D irradiation plan was used to verify the location of a new tumor deposit within the path of a brachytherapy catheter at the time of treatment. Results: We identified 9 needle track metastases, corresponding to a catheter-based risk of 1.5% for any location of occurrence. A total of 7 metastases were located within the liver (catheter-based risk, 1.2%), and 2 metastases were located extrahepatic (catheter-based risk, 0.3%). Eight out of 9 needle track metastases were successfully treated by further HDR-BT. Conclusions: The risk for needle track seeding after interstitial HDR-BT of HCC is comparable to previous reports of percutaneous biopsies and radiofrequency ablation (RFA), especially in case of extrahepatic needle track metastases. To compensate for the risk of seeding, a track irradiation technique similar to track ablation in RFA should be implemented in clinical routine.

Purpose To evaluate efficacy and safety of CT-guided iBT in patients with primary and secondary malignancies of the pancreas. Material and methods 13 patients with 13 lesions of the pancreatic corpus and tail were included: 8 secondary malignancies (metastatic lesions = ML) and 5 primary malignancies, including 3 primary tumors (PT) and 2 isolated locoregional recurrences (ILR) after surgical resection were treated with image-guided iBT using a 192iridium source (single fraction irradiation). Every 3 months after treatment clinical and imaging follow-up were conducted to evaluate efficacy. Peri- and postinterventional complications were assessed descriptively. Results The median diameter of the gross tumor volume (GTV) was 3 cm (range 1–6.5 cm), treated with a median D100 (minimal enclosing tumor dose) of 15.3 Gy (range 9.2–25.4 Gy). Local tumor control (LTC) was 92.3% within a median follow-up period of 6.7 months (range 3.2–55.7 months). Cumulative median progression free survival (PFS) was 6.2 months (range 2.8–25.7 months; PFS of primary and secondary malignancies was 5.8 and 6.2 months, respectively). Cumulative median over all survival (OS) after iBT was 16.2 months (range 3.3–55.7 months; OS of primary and secondary malignancies was 7.4 months and 45.6 months, respectively). 1 patient developed mild acute pancreatits post iBT, spontanously resolved within 1 week. No severe adverse events (grade 3+) were recorded. Conclusion Image-guided iBT is a safe and particularly effective treatment in patients with primary and secondary malignancies of the pancreas and might provide a well-tolerated additional therapeutic option in the multidisciplinary management of selected patients.

Purpose Organs at risk (OARs), which are very close to a clinical target volume (CTV), can compromise effective tumor irradiation. The present study investigated the feasibility and safety of a novel approach, in particular, the extent of the dosimetric effect of distancing CTV from adjacent OARs by means of interventionally applied balloon catheters. Material and methods Patients with peripheral hepatic malignancies, in whom the critical proximity of an OAR to the CTV in the assessment by contrast-enhanced magnetic resonance imaging (MRI) scans and the preplanning process were included. Additionally, patients underwent placement of an interventional balloon catheter during computed tomography (CT)-guided application of interstitial brachytherapy (iBT) catheters inserted into the tissue between hepatic capsule and adjacent OAR. The virtual position of an OAR without balloon catheter was anticipated and contoured in addition to contouring of CTV and OAR. The calculated dose values for CTV as well as 1 cc of the relevant OAR (D1cc) with and without balloon were recorded. The D1cc of the realized irradiation plan was statistically compared to the D1cc of the virtually contoured OARs. Results In 31 cases, at least one balloon catheter was administered. The mean D1cc of the OAR in the group with balloon(s) was 12.6 Gy compared with 16 Gy in the virtual cohort without the device, therefore significantly lower (p < 0.001). Overall, there were no acute complications. Severe (> 2 CTCAEv4.03) late complications observed in 3/31 (9.6%) patients during follow-up period after brachytherapy were most certainly not due to the balloon application. Side effects were probably associated with pre-existing serious diseases and potentially additional local late effects of the irradiation in general rather than with the balloon catheters. Conclusions The distancing of the adjacent OARs allows a higher D100 value of CTV, therefore allowing for more efficient local control.

Image-guided high-dose-rate interstitial brachytherapy (iBT) with iridium-192 is an effective treatment option for patients with liver malignancies. Little is known about long-term radiation effects on the bile duct system when central hepatic structures are exposed to iBT. This retrospective analysis investigates the occurrence of posthepatic cholestasis (PHC) and associated complications in patients undergoing iBT. We identified patients who underwent iBT of hepatic malignancies and had point doses of ≥1 Gy to central bile duct structures. Patients with known bile duct-related diseases or prior bile duct manipulation were excluded. 102 patients were retrospectively included. Twenty-two patients (22%) developed morphologic PHC after a median of 17 (3–54) months; 18 of them were treated using percutaneous transhepatic cholangiopancreatography drainage or endoscopic retrograde cholangiopancreatography. The median point dose was 24.8 (4.4–80) Gy in patients with PHC versus 14.2 (1.8–61.7) Gy in those without PHC (p = 0.028). A dose of 20.8 Gy (biological effective dose, BED3/10 = 165/64.1 Gy) was identified to be the optimal cutoff dose (p = 0.028; 59% sensitivity, 24% specificity). Abscess/cholangitis was more common in patients with PHC compared to those without (4 of 22 vs. 2 of 80; p = 0.029). Median survival did not differ between patients with and without PHC (43 vs. 36 months; p = 0.571). iBT of liver malignancies located near the hilum can cause PHC when the central bile ducts are exposed to high point doses. Given the long latency and absence of impact of iBT-induced PHC on median survival, the rate of cholestasis and complications seen in our patients appears to be acceptable.

Purpose Computed tomography (CT) or magnetic resonance imaging (MRI) guided brachytherapy provides high tumor control rates in hepatocellular carcinoma (HCC) and colorectal liver metastases. In contrast to thermal ablation methods such as radiofrequency ablation (RFA), much less restrictions apply with respect to tumor location or size. In this study, we determined the efficacy and safety of CT- or MRI-guided brachytherapy in metastatic melanoma. Material and methods Fifty-two metastases of malignant melanoma in 14 patients were included in this retrospective study. Local tumor control and safety were evaluated as primary and secondary endpoints. Furthermore, we evaluated overall survival and progression free survival. Tumor locations were liver (n = 31), lung (n = 15), adrenal (n = 3), lymph nodes (n = 2), and kidney (n = 1). Treatment planning was performed using three-dimensional CT or MRI data acquired after percutaneous applicator positioning under CT or open MRI guidance. Subsequently, single fraction high-dose-rate (HDR) brachytherapy was applied using a (192)Iridium source. Clinical and cross-sectional follow-up were performed every 3 months post intervention. Results The median diameter of treated lesions was 1.5 cm (range: 0.7-10 cm). Doses between 15 and 20 Gy were applied (median dose: 19.9 Gy). The mean irradiation time ranged between 7-45 minutes. After treatment, there was one patient with a cholangitis. After a median follow up of five months, the median local tumor control was 90%. The median overall survival of the patients was 8 months. The median progression free survival of the patients was 6 months. Conclusions Image-guided HDR brachytherapy is a safe and effective treatment procedure in metastatic malignant melanoma.

Perfusion scintigraphy using 99mTc-labeled albumin aggregates is mandatory before hepatic radioembolization with 90Y-microspheres. As part of a prospective trial, the intrahepatic and intrapulmonary stability of 2 albumin compounds, 99mTc-MAA (macroaggregated serum albumin [MAA]) and 99mTc-HSA (human serum albumin [HSA]), was assessed. Methods: In 24 patients with metastatic colorectal cancer, biodistribution (liver, lung) and liver–lung shunt (LLS) of both tracers (12 patients each) were assessed by sequential planar scintigraphy (1, 5, and 24 h after injection). Results: Liver uptake of both albumin compounds decreased differently. Although initial LLSs at 1 h after injection were similar in both groups, MAA-LLS increased significantly from 1 (3.9%) to 5 h (7.7%) and 24 h (9.9%) after injection, respectively. HSA-LLS did not change significantly (1 to 5 h), indicating a steady state of pulmonary and intrahepatic degradation. Conclusion: Compared with 99mTc-MAA-microspheres, 99mTc-HSA-microspheres are likely more resistant to degradation over time, allowing a reliable LLS determination even at later time points.

While local treatment using more innovative technologies is increasingly applied in contemporary treatment of advanced cancer, its impact on outcomes is not well understood.We reviewed the literature using PubMed and major oncology congress websites, and report here about the understanding of oligometastatic disease, about the role of primary tumor resection in metastatic disease, and about the value of cytoreduction and tumor ablation.The Achilless' heel of local treatment is the current lack of evidence of its efficacy. When considering how this lack of knowledge can be overcome, we arrive at three suggestions: First, adequately powered clinical trials must be performed to allow for the proper assessment of differences in survival outcomes. Second, the effect of local treatment on the biological evolution of the disease needs to be studied; analysis of circulating tumor DNA may help to assess these effects. Third and foremost, patient-reported outcomes like quality of life, symptom control, and satisfaction with treatment should define when to use and when to omit local treatment.Innovative trial designs in future oncology research will be required for assessing the true value of local and locoregional therapy.Während lokale Tumorbehandlung mit innovativen Technologien einen zunehmenden Raum in der heutigen Therapie fortgeschrittener Tumorerkrankungen einnimmt, ist ihre Bedeutung für die Ergebnisverbesserung weiterhin schlecht definiert.Wir führten eine Literatursichtung über PubMed und große Onkologie-Kongress-Websites durch und berichten über das derzeitige Verständnis der oligometastasierten Erkrankung, die Rolle der Primärtumorresektion bei metastasierter Erkrankung und über den Stellenwert von Zytoreduktion und Tumorablation.Die Achillesferse der Lokalbehandlung ist die derzeit mangelhafte Evidenz für ihre Wirksamkeit. In Überlegung, wie dieser Mangel beseitigt werden kann, unterbreiten wir drei Vorschläge: Erstens müssen ausreichend große klinische Studien durchgeführt werden, welche die saubere Erfassung lebenszeitbezogener Unterschiede erlauben. Zweitens müssen die Auswirkungen einer Lokalbehandlung auf die biologische Evolution der Erkrankung untersucht werden. Die Analyse zirkulierender Tumor-DNA könnte hilfreich sein, um diese Effekte zu verstehen. Drittens, besonders wichtig ist die Erfassung patientenberichteter Veränderungen im Bereich der Lebensqualität, Symptomkontrolle und Behandlungszufriedenheit. Diese Ergebnisse sollten den Weg weisen, in welcher Situation in Zukunft lokoregionale Behandlung angewendet und wann sie unterlassen werden sollte.Wir benötigen für die Onkologie von morgen innovative Studiendesigns, um den wahren Stellenwert lokaler und lokoregionaler Behandlungsverfahren zu bestimmen.

OBJECTIVES The aims of this study were to develop magnetic resonance (MR)-guided freehand radiofrequency ablation (RFA) using a near-real-time interactive MR platform in an open 1.0-T MR scanner and to determine the feasibility and safety of this new approach in the clinical setting. METHODS The study was performed using an open 1.0-T MR system and a low-pass filter to prevent interaction between the RFA generator and the scanner. Artifact size of the radiofrequency needle was measured in 2 perpendicular views (transversal [tra] and coronal [cor]) in vitro and in the tra orientation in vivo for diagnostic (T1 high resolution isotropic volume excitation [THRIVE]/T2 turbo spin-echo [TSE]) and near-real-time (T1 fast-field-echo [FFE]) imaging. A liver-specific contrast medium (gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid) was administered 20 minutes before the intervention to enhance lesion visibility. Visibility was rated and compared for both interventional and diagnostic imaging sequences using a 10-point grading scale. Intervention time and complications were recorded. RESULTS The mean diameter of needle artifact size for interventional T1 FFE was 17.4 ± 0.7 mm (tra) and 17.1 ± 1.1 mm (cor) in vitro and 15.2 ± 1.5 mm (tra) in vivo. Artifact size for diagnostic imaging was 12.5 ± 1.8 mm (tra) and 11.2 ± 1.4 mm (cor) in vitro and 10.5 ± 1.7 mm in vivo using THRIVE and 8.1 ± 2.4 mm (tra) and 10.8 ± 1.8 mm (cor) in vitro and 9.7 ± 2.0 mm (tra) in vivo using T2 TSE. A total of 57 patients with liver malignancies (mean tumor size, 17 ± 7 mm) underwent freehand MR-guided RFA. In all patients, the ablative procedure was technically successful. Lesion visibility of the diagnostic T2 TSE sequence (4 ± 2) was significantly decreased compared with both the diagnostic (THRIVE, 7 ± 2) and interventional (T1 FFE, 8 ± 1) T1-weighted sequences. Mean time to position the applicator was 7.5 ± 2 minutes. Procedure times ranged from 30 to 60 minutes. The mean in-room time was 57 ± 22 minutes. No major complications were recorded. CONCLUSIONS Magnetic resonance-guided freehand RFA using a near-real-time interactive MR platform in an open 1.0-T MR scanner is feasible, safe, and applicable in clinical routine. The administration of a hepatocyte-specific contrast agent enhances lesion visualization and therefore improves targeting. Without the need for additional sophisticated devices, this new approach simplifies and shortens the RFA procedure compared with previously published methods.

To assess the efficacy, safety, and outcome of image-guided high-dose-rate (HDR) brachytherapy in patients with adrenal gland metastases (AGM). From January 2007 to April 2014, 37 patients (7 female, 30 male; mean age 66.8 years, range 41.5–82.5 years) with AGM from different primary tumors were treated with CT-guided HDR interstitial brachytherapy (iBT). Primary endpoint was local tumor control (LTC). Secondary endpoints were time to untreatable progression (TTUP), time to progression (TTP), overall survival (OS), and safety. In a secondary analysis, risk factors with an influence on survival were identified. The median biological equivalent dose (BED) was 37.4 Gy. Mean LTC after 12 months was 88%; after 24 months this was 74%. According to CTCAE criteria, one grade 3 adverse event occurred. Median OS after first diagnosis of AGM was 18.3 months. Median OS, TTUP, and TTP after iBT treatment were 11.4, 6.6, and 3.5 months, respectively. Uni- and multivariate Cox regression analyses revealed significant influences of synchronous disease, tumor diameter, and the total number of lesions on OS or TTUP or both. Image-guided HDR-iBT is safe and effective. Treatment- and primary tumor-independent features influenced survival of patients with AGM after HDR-iBR treatment.

The aim of this study was to assess the rates of haemorrhagic and thrombotic complications in patients undergoing interventional tumour ablation with and without peri-interventional low-molecular-weight heparin (LMWH) thrombosis prophylaxis. Patients presented with primary and secondary neoplastic lesions in the liver, lung, kidney, lymph nodes and other locations. A total of 781 tumour ablations (radiofrequency ablation, n = 112; interstitial brachytherapy, n = 669) were performed in 446 patients over 22 months; 260 were conducted under peri-interventional thrombosis prophylaxis with LMWH (H-group;) and 521 without this (NH-group, in 143 of these, LMWH was given post-interventionally). Sixty-three bleeding events occurred. There were significantly more bleedings in the H-group than in the NH-group (all interventions, 11.66 and 6.26 %, p = 0.0127; liver ablations, 12.73 and 7.1 %, p = 0.0416). The rate of bleeding events Grade ≥ III in all procedures was greater by a factor of >2.6 in the H-group than in the NH-group (4.64 and 1.73 %, p = 0.0243). In liver tumour ablations, the corresponding factor was about 3.3 (5.23 and 1.54 %, p = 0.028). In uni- and multivariate analyses including covariates, the only factor constantly and significantly associated with the rate of haemorrhage events was peri-interventional LMWH prophylaxis. Only one symptomatic lung embolism occurred in the entire cohort (NH-group). The 30- and 90-day mortalities were significantly greater in the H-group than in the NH-group. Peri-interventional LMWH thrombosis prophylaxis should be considered with caution. The rate of clinically relevant thrombotic events was extremely low.

Background In treatment-refractory liver dominant metastatic colorectal cancer, the role of liver directed therapies still is unclear. We sought to determine a prognostic score for Y90 radioembolization in these patients. Methods We analyzed 106 patients with refractory liver dominant mCRC who had undergone a total of 178 Y90 radioembolizations with resin microspheres was collected. Potential factors influencing survival were analyzed using a Cox regression. The Log rank test served to establish prognostic factors and to form a clinical score for outcome prediction after Y90 radioembolization. Results Median survival of all patients was 6.7 months. Neither age nor prior surgical or systemic therapy nor metastatic spread had an effect on survival. In contrast, hepatic tumor load, Karnofsky index as well as CEA and CA19-9 serums level had a significant influence (p 20 %, CEA >130 ng/ml or CA19-9 > 200U/ml and Karnofsky index

BACKGROUND: As standard bolus triggering in the pulmonary trunk sometimes fails to achieve sufficient enhancement in the pulmonary arteries, the study investigates an alternative, 'delayed' position of the tracking ROI in the descending aorta. MATERIAL AND METHODS: Retrospective analysis of 143 patients suspected of pulmonary embolism investigated with 3 different scanners (16 to 80 rows) in clinical routine. Bolus triggering with 120 hounsfield units (HU) was performed using the pulmonary trunk (n=70) or descending aorta (n=73) after application of 70 to 120 mL of contrast agent, Iomeprol 300. Student's t-test was applied to compare vascular enhancement. Additional factors were analysed by a regression analysis. RESULTS: Positioning of the tracking ROI in the descending aorta achieved a significantly higher contrast enhancement in the pulmonary trunk with a mean increase of 63 HU (p

High-dose rate brachytherapy for primary and secondary liver malignancies is an innovative radio-oncological modality enjoying rapid acceptance and adoption in the field of interventional oncology. It is a safe and effective treatment most useful in the salvage situation in patients with large hepatic tumors or an intermediate number of lesions unsuitable for thermal ablation or stereotactic external radiotherapy. In this chapter the radiobiological and technical aspects of CT-guided brachytherapy for the treatment of liver cancers are discussed. Clinical toxicity and efficacy outcomes after this technique are described including a comprehensive data review.

This study was designed to evaluate overall survival after radioembolization or best supportive care (BSC) in patients with chemotherapy-refractory liver-dominant metastatic colorectal cancer (mCRC). This was a matched-pair comparison of patients who received radioembolization plus BSC or BSC alone for extensive liver disease. Twenty-nine patients who received radioembolization were retrospectively matched with a contemporary cohort of >500 patients who received BSC from 3 centers in Germany. Using clinical databases, patients were initially matched for prior treatments and tumor burden and then 29 patients were consecutively identified with two or more of four matching criteria: synchronous/metachronous metastases, tumor burden, increased ALP, and/or CEA >200 U/ml. Survival was calculated from date of progression before radioembolization or BSC by using Kaplan–Meier analysis. Of 29 patients in each study arm, 16 pairs (55.2%) matched for all four criteria, and 11 pairs (37.9%) matched three criteria. Patients in both groups had a similar performance status (Karnofsky index, median 80% [range, 60–100%]). Compared with BSC alone, radioembolization prolonged survival (median, 8.3 vs. 3.5 months; P

To determine local tumor control after CT-guided brachytherapy at various dose levels and the prognostic impact of extensive cytoreduction in colorectal liver metastases.Seventy-three patients were treated on a single-center prospective trial that was initially designed to be randomized to three dose levels of 15 Gy, 20 Gy, or 25 Gy per lesion, delivered in a single fraction. However, because there was a high rate of cross-over of subjects from higher to lower dose levels, this study is better understood as a prospective trial with three dose levels. No upper size limit for the metastases was applied. We assessed time to local progression, progression-free survival, and overall survival.According to safety constraints cross-over was performed. The final assignment was n = 98, n = 68, and n = 33 in the 15-Gy, 20-Gy, and 25-Gy groups, respectively. Median diameter of the largest tumor lesion in each patient was 5 cm (range, 1-13.5 cm). Estimated mean local recurrence-free survival for all lesions was 34 months (median not reached). The group assigned to 15 Gy after cross-over displayed 34 local recurrences out of 98 lesions; 20 Gy, 15 out of 68 lesions; 25 Gy, 1 out of 33 lesions. The difference between the 25-Gy and the 20-Gy or 15-Gy group was significant (p0.05). Repeated local tumor ablations were the most prominent factor for increased survival and dominated additional systemic antitumor treatments.Local tumor control after CT-guided brachytherapy of colorectal liver metastases demonstrated a strong dose dependency. The role of extensive minimally invasive tumor ablation in metastatic colorectal cancer needs to be further established.

Image guided minimally invasive local and locoregional tumor ablation techniques like radiofrequency ablation, interstitial brachytherapy, transarterial chemoembolization (TACE) and selective internal radiotherapy (SIRT) with (90)Yttrium ( (90)Y) microspheres have been established as valuable amendments in oncologic therapy concepts. These techniques allow the destruction of extensive liver tumors with an acceptable toxicity profile. Necessity for a safe performance of these procedures is a close collaboration between interventional radiologist and anesthetist.

New interventional options especially for patients with HCC and BCLC scores B and C give rise to disputes about the optimal therapeutic management. CT-guided brachytherapy complements established interventional techniques like RFA and TACE since it may also be used successfully in tumors much greater than 5 cm in diameter. In addition, unlike thermal ablation, the brachytherapy technique may be applied in tumors located nearby risk structures such as liver hilum or gallbladder and it is independent of cooling effects such as through large blood vessels or strong tumor perfusion. Depending on tumor size, geometry and visibility, MRI or CT guidance may be used. 15 Gy minimal target dose can be applied safely in a single or – in case of very large tumors – a sequential approach targeting different tumor portions. Local recurrence rates will be very low, and the rate of complications is moderate despite the fact that most patients present with underlying cirrhosis and related comorbidities. Preliminary data suggest a positive impact on overall survival. Randomized controlled trials are on their way to assess combination schemes with systemic treatments such as sorafenib.

To compare local tumor control after percutaneous tumor ablation by interstitial laser therapy (ILT) or CT-guided brachytherapy (CTGB). In a matched pair analysis including 18 patients with 36 liver metastases of colorectal primary, both ILT and CTGB were performed in different lesions. The following matching factors were considered: (i) tumor size ≤ 5 cm, and (ii) execution of chemotherapy after tumor ablation. Primary endpoint was local tumor control. Treated lesions were identical in terms of tumor size and all matching criteria were fulfilled in all patients except for the performance of adjuvant chemotherapy. Median follow-up was 14 months (3–24 months) for both groups. Only five of 18 patients (28%) demonstrated local tumor progression after CTGB, whereas in ten of 18 patients (56%) tumor progression was found after ILT. Differences encountered were significant for all patients (p = 0.04), whereas in those who fulfilled all matching criteria (n = 14) the level of statistical significance was not reached (p = 0.23). CTGB demonstrated superior local tumor control compared to ILT in long-term follow-up.

Aim. To assess the outcomes of patients with unresectable intrahepatic cholangiocellular carcinoma (ICC) treated by a tailored therapeutic approach, combining systemic with advanced image-guided local or locoregional therapies.Materials and Methods. Treatment followed an algorithm established by a multidisciplinary GI-tumor team. Treatment options comprised ablation (RFA, CT-guided brachytherapy) or locoregional techniques (TACE, radioembolization, i.a. chemotherapy).Results. Median survival was 33.1 months from time of diagnosis and 16.0 months from first therapy. UICC stage analysis showed a median survival of 15.9 months for stage I, 9 months for IIIa, 18.4 months for IIIc, and 13 months for IV. Only the number of lesions, baseline serum CEA and serum CA19-9, and objective response (RECIST) were independently associated with survival. Extrahepatic metastases had no influence.Conclusion. Patients with unresectable ICC may benefit from hepatic tumor control provided by local or locoregional therapies. Future prospective study formats should focus on supplementing systemic therapy by classes of interventions (“toolbox”) rather than specific techniques, that is, local ablation leading to complete tumor destruction (such as RFA) or locoregional treatment leading to partial remission (such as radioembolization). This trial is registered with German Clinical Trials Registry (Deutsche Register Klinischer Studien), DRKS-ID:DRKS00006237.

To evaluate complications and identify risk factors for adverse events in patients undergoing high-dose-rate interstitial brachytherapy (iBT). Data from 192 patients treated in 343 CT- or MRI-guided interventions from 2006–2009 at our institution were analyzed. In 41 %, the largest tumor treated was ≥ 5 cm, 6 % of the patients had tumors ≥ 10 cm. Prior to iBT, 60 % of the patients had chemotherapy, 22 % liver resection, 19 % thermoablation or transarterial chemoembolization (TACE). Safety was the primary endpoint; survival data were obtained as the secondary endpoints. During follow-up, MRI or CT imaging was performed and clinical and laboratory parameters were obtained. The rate of major complications was below 5 %. Five major bleedings (1.5 %) occurred. The frequency of severe bleeding was significantly higher in patients with advanced liver cirrhosis. One patient developed signs of a nonclassic radiation-induced liver disease. In 3 patients, symptomatic gastrointestinal (GI) ulcers were detected. A dose exposure to the GI wall above 14 Gy/ml was a reliable threshold to predict ulcer formation. A combination of C-reactive protein ≥ 165 mg/l and/or leukocyte count ≥ 12.7 Gpt/l on the second day after the intervention predicted infection (sensitivity 90.0 %; specificity 92.8 %.) Two patients (0.6 %) died within 30 days. Median overall survival after the first liver treatment was 20.1 months for all patients and the local recurrence-free surviving proportion was 89 % after 12 months. Image-guided iBT yields a low rate of major complications and is effective.

Metastatic spread of the primary is still defined as the systemic stage of disease in treatment guidelines for various solid tumors. This definition is the rationale for systemic therapy. Interestingly and despite the concept of systemic involvement, surgical resection as a local treatment has proven to yield long-term outcomes in a subset of patients with limited metastatic disease, supporting the concept of oligometastatic disease. Radiofrequency ablation has yielded favorable outcomes in patients with hepatocellular carcinoma and colorectal metastases, and some studies indicate its prognostic potential in combined treatments with systemic therapies. However, some significant technical limitations apply, such as size limitation, heat sink effects, and unpredictable heat distribution to adjacent risk structures. Interventional and non-invasive radiotherapeutic techniques may overcome these limitations, expanding the options for oligometastatic patients and cytoreductive concepts. Current data suggest very high local control rates even in large tumors at any given location in the human body. The article focusses on the characteristics and possibilities of stereotactic body radiation therapy, interstitial high-dose-rate brachytherapy, and Yttrium-90 radioembolization. In this article, we discuss the differences of the technical preferences as well as their impact on indications. Current data is presented and discussed with a focus on application in oligometastatic or cytoreductive concepts in different tumor biologies.In den Leitlinien zur Behandlung verschiedener solider Tumoren wird die Metastasierung des Primärtumors nach wie vor als das systemische Stadium der Erkrankung definiert. Diese Definition begründet das Vorgehen für eine systemische Therapie. Interessanterweise, und trotz des Konzepts der systemischen Beteiligung, hat die chirurgische Resektion als lokale Behandlungsmöglichkeit langfristige Ergebnisse in einer Untergruppe von Patienten mit begrenzter Metastasierung zeigen können; dies bekräftigt das Konzept der oligometastatischen Erkrankung. Die Radiofrequenzablation hat günstige Ergebnisse bei Patienten mit Leberzellkarzinom und kolorektalen Metastasen gezeigt, und einige Studien weisen ihr prognostisches Potenzial bei mit systemischen Therapien kombinierten Behandlungen auf. Allerdings gelten hierbei einige wichtige technische Einschränkungen, wie z.B. Größenbeschränkung, «heat sink»-Effekte und unvorhersehbare Wärmeverteilung auf benachbarte Risikostrukturen. Interventionelle und nichtinvasive radiotherapeutische Techniken können diese Einschränkungen überwinden und hierdurch die Optionen für oligometastatische Patienten und für zytoreduktive Konzepte erweitern. Aktuelle Daten deuten auf sehr hohe lokale Kontrollraten auch bei großen Tumoren an jedem Ort im menschlichen Körper hin. Dieser Artikel befasst sich mit den Charakteristika und Möglichkeiten der stereotaktischen (Körper-)Radiotherapie, der interstitiellen hochdosierten Brachytherapie und der Yttrium-90-Radioembolisation. Wir diskutieren in diesem Beitrag die Unterschiede der technischen Präferenzen sowie ihre Auswirkungen auf die Indikationen. Aktuelle Daten werden vorgestellt und mit einem Fokus auf die Anwendung in oligometastatischen oder zytoreduktiven Konzepten bei unterschiedlichen Tumorbiologien diskutiert.

Methods: Fifteen patients (f, 6; m, 9; median age, 59 years; range, 32 to 72 years) with 28 liver metastases were included retrospectively. FDG-PET/CT imaging (median activity, 237 MBq; range, 231 to 252 MBq; median uptake, 61 min; range, 55 to 67 min) was performed on a Siemens Biograph mCT 64 followed by image reconstruction using 3D-ordered subset expectation maximization (3D-OSEM) or 3D-OSEM with PSF modeling - both with and without TOF information. Differences in SUVmax were analyzed using the Friedman test and Wilcoxon test for paired non-parametric data. The correlation of inter-method differences with the lesions’ TBR was studied using Spearman’s rank correlation coefficient (rho). Differences between lesions with low (4.8) TBR were analyzed using the Mann-Whitney U test (TBR measured with 3D-OSEM; binarized by its median). Background: The maximum standardized uptake value (SUVmax) is a common clinical parameter for quantification in F18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), but it is influenced by image reconstruction. The aim of this study was to analyze the association of SUVmax deviations related to point spread function (PSF) and time-of-flight (TOF) reconstruction with tumor-to-background ratios (TBR) in colorectal liver metastases (CRLM). Results: There was a significant correlation of the lesions’ TBR with relative SUVmax differences related to PSF (PSF + TOF vs. 3D-OSEM + TOF, rho = 0.61; PSF vs. 3D-OSEM, rho = 0.52) or TOF (PSF + TOF vs. PSF, rho = −0.58; 3D-OSEM + TOF vs. 3D-OSEM, rho = −0.61). Accordingly, PSF algorithms only showed higher SUVmax than non-PSF algorithms in lesions with a high TBR (median differences at low/high TBR, +2.6%/+9.1% [PSF + TOF vs. 3D-OSEM + TOF]; +0.7%/+6.4% [PSF vs. 3D-OSEM]). TOF integration also led to higher SUVmax but mainly at low TBR (low/high TBR, +10.4%/+1.8% [PSF + TOF vs. PSF]; +8.6%/−0.1% [3D-OSEM + TOF vs. 3D-OSEM]). Conclusions: Both PSF and TOF reconstruction resulted in a substantial alteration of SUVmax in CRLM. TOF provided the highest SUVmax increase in low-contrast lesions while - vice versa - PSF showed the most relevant increase in high-contrast lesions. Thus, one should be aware that quantitative analyses of lesions with varying TBR, e.g., in radiotherapy or follow-up studies, may be mainly affected by either PSF or TOF reconstruction, respectively.

Purpose: To prospectively assess a dose-response relationship for small volumes of liver parenchyma after single-fraction irradiation. Methods and Materials: Twenty-five liver metastases were treated by computed tomography (CT)-guided interstitial brachytherapy. Magnetic resonance imaging was performed 1 day before and 3 days and 6, 12, and 24 weeks after therapy. MR sequences included T1-w gradient echo (GRE) enhanced by hepatocyte-targeted gadobenate dimeglumine. All MRI data sets were merged with 3D dosimetry data and evaluated by two radiologists. The reviewers indicated the border of hyperintensity on T2-w images (edema) or hypointensity on T1-w images (loss of hepatocyte function). Based on the total 3D data, a dose-volume histogram was calculated. We estimated the threshold dose for either edema or function loss as the D 90 , i.e., the dose achieved in at least 90% of the pseudolesion volume. Results: Between 3 days and 6 weeks, the extension of the edema increased significantly from the 12.9 Gy isosurface to 9.9 Gy (standard deviation [SD], 3.3 and 2.6). No significant change was detected between 6 and 12 weeks. After 24 weeks, the edematous tissue had shrunk significantly to 14.7 Gy (SD, 4.2). Three days postbrachytherapy, the D 90 for hepatocyte function loss reached the 14.9 Gy isosurface (SD, 3.9). At 6 weeks, the respective zone had increased significantly to 9.9 Gy (SD, 2.3). After 12 and 24 weeks, the dysfunction volume had decreased significantly to the 11.9 Gy and 15.2 Gy isosurface, respectively (SD, 3 and 4.1). Conclusions: The 95% interval from 7.6 to 12.2 Gy found as the minimal hepatocyte tolerance after 6 weeks accounts for the radiobiologic variations found in CT-guided brachytherapy, including heterogeneous dose rates by variable catheter arrays.

The purpose of this study was to assess the safety of repeated 90Y radioembolization with resin microspheres in patients with extensive primary and secondary liver tumors after failure of first radioembolization. Methods: Between 2007 and 2011, 21 patients (12 women, 9 men; mean age, 61.0 y) with nonresectable advanced liver tumors (breast cancer liver metastases, n = 7; colorectal liver metastases, n = 5; hepatocellular carcinoma, n = 8; cholangiocellular carcinoma, n = 1) were repeatedly treated by radioembolization. Safety was the primary endpoint. Whole-liver treatment was achieved with sequential treatment sessions in most patients, with selective embolization of the left and right liver lobes within 6 wk. Toxicity was documented prospectively and according to Common Terminology Criteria for Adverse Events 4.0 criteria based on laboratory parameters; magnetic-resonance tomography; and clinical examinations 3 d, 6 wk, and every 3 mo after selective internal radiotherapy (SIRT). Metric variables were evaluated using the Student t test. Overall survival was assessed by Kaplan–Meier statistics. Results: Patients received an average of 1.6 whole-liver treatments performed in 3.0 unilobar radioembolizations (liver lobes sequentially). The mean total activity administered was 2.57 GBq. No radioembolization-induced liver disease was observed in any of the patients. Three patients showed reversible grade III to IV toxicities according to laboratory values, which returned to pretreatment levels after 6 wk. In 1 patient, a treatment-related duodenal ulcer occurred. Median overall survival was 18 mo after first radioembolization. Conclusion: In advanced liver tumors, repeated whole-liver treatments with 90Y radioembolization can be performed with an acceptable toxicity profile.

Background/Aim: Targeted radiotherapy of liver malignancies has found to be effective in selected patients. A key limiting factor of these therapies is the relatively low tolerance of the liver parenchyma to radiation. We sought to assess the preventive effects of a combined regimen of pentoxifylline (PTX), ursodeoxycholic acid (UDCA) and low-dose low molecular weight heparin (LMWH) on focal radiation-induced liver injury (fRILI). Methods and Materials: Patients with liver metastases from colorectal carcinoma who were scheduled for local ablation by radiotherapy (image-guided high-dose-rate interstitial brachytherapy) were prospectively randomized to receive PTX, UDCA and LMWH for 8 weeks (treatment) or no medication (control). Focal RILI at follow-up was assessed using functional hepatobiliary magnetic resonance imaging (MRI). A minimal threshold dose, i.e. the dose to which the outer rim of the fRILI was formerly exposed to, was quantified by merging MRI and dosimetry data. Results: Results from an intended interim-analysis made a premature termination necessary. Twenty-two patients were included in the per-protocol analysis. Minimal mean hepatic threshold dose 6 weeks after radiotherapy (primary endpoint) was significantly higher in the study treatment-group compared with the control (19.1 Gy versus 14.6 Gy, p=0.011). Qualitative evidence of fRILI by MRI at 6 weeks was observed in 45.5% of patients in the treatment versus 90.9% of the control group. No significant differences between the groups were observed at the 12-week follow-up. Conclusions: The post-therapeutic application of PTX, UDCA and low-dose LMWH significantly reduced the extent and incidence fRILI at 6 weeks after radiotherapy. The development of subsequent fRILI at 12 weeks (4 weeks after cessation of PTX, UDCA and LMWH during weeks 1–8) in the treatment group was comparable to the control group thus supporting the observation that the agents mitigated fRILI. Trial Registration: EU clinical trials register 2008-002985-70 ClinicalTrials.gov NCT01149304

Radiotherapy of liver malignancies shows promising results (radioembolization, stereotactic irradiation, interstitial brachytherapy). Regardless of the route of application, a certain amount of nontumorous liver parenchyma will be collaterally damaged by radiation. The functional reserve may be significantly reduced with an impact on further treatment planning. Monitoring of radiation-induced liver damage by imaging is neither established nor validated. We performed an analysis to correlate the histopathological presence of radiation-induced liver damage with functional magnetic resonance imaging (MRI) utilizing hepatobiliary contrast media (Gd-BOPTA). Patients undergoing local high-dose-rate brachytherapy for whom a follow-up hepatobiliary MRI within 120 days after radiotherapy as well as an evaluable liver biopsy from radiation-exposed liver tissue within 7 days before MRI were retrospectively identified. Planning computed tomography (CT)/dosimetry was merged to the CT-documentation of the liver biopsy and to the MRI. Presence/absence of radiation-induced liver damage (histopathology) and Gd-BOPTA uptake (MRI) as well as the dose applied during brachytherapy at the site of tissue sampling was determined. Fourteen biopsies from eight patients were evaluated. In all cases with histopathological evidence of radiation-induced liver damage (n = 11), no uptake of Gd-BOPTA was seen. In the remaining three, cases no radiation-induced liver damage but Gd-BOPTA uptake was seen. Presence of radiation-induced liver damage and absence of Gd-BOPTA uptake was correlated with a former high-dose exposition. Absence of hepatobiliary MRI contrast media uptake in radiation-exposed liver parenchyma may indicate radiation-induced liver damage. Confirmatory studies are warranted.

Noninvasive imaging has become the standard for hepatocellular carcinoma (HCC) diagnosis in cirrhotic patients. Typical imaging features of HCC such as arterial wash-in and venous wash-out deliver very high specificity and acceptable sensitivity even in nodules from 1 to 2 cm in diameter. However, limitations apply specifically in hypovascular HCC, for which the addition of new techniques such as diffusion-weighted magnetic resonance imaging (DW-MRI) or hepatobiliary MRI is helpful. Whereas DW-MRI adds to both the sensitivity and specificity, hepatobiliary MRI additionally contributes valuable information in cirrhotic patients on the histopathology of small lesions, including early HCC and high-grade dysplastic nodules. Biopsy of small, atypical lesions is associated with a high rate of false-negative findings and should be used only after careful consideration in selected patients. Here, we review the current international guidelines on HCC diagnosis as well as the latest developments in imaging that may contribute to safe detection and accurate characterization of suspicious nodules in patients with liver cirrhosis.

In patients with liver malignancies potentially amenable to curative extended right hepatectomy but insufficient size of the future liver remnant (FLR), portal vein embolization (PVE) of the tumor-bearing liver is used to induce contralateral liver hypertrophy but leaves the tumor untreated. Radioembolization (RE) treats the tumor in the embolized lobe along with contralateral hypertrophy induction. We performed a matched-pair analysis to compare the capacity for hypertrophy induction of these two modalities. Patients with right-hepatic secondary liver malignancies with no or negligible left-hepatic tumor involvement who were treated by right-lobar PVE (n = 141) or RE (n = 35) at two centers were matched for criteria known to influence liver regeneration following PVE: 1) baseline FLR/Total liver volume ratio (

Background To assess brachytherapy catheter positioning accuracy and to evaluate the effects of prolonged irradiation time on the tolerance dose of normal liver parenchyma following single-fraction irradiation with 192 Ir. Materials and methods Fifty patients with 76 malignant liver tumors treated by computed tomography (CT)-guided high-dose-rate brachytherapy (HDR-BT) were included in the study. The prescribed radiation dose was delivered by 1 - 11 catheters with exposure times in the range of 844 - 4432 seconds. Magnetic resonance imaging (MRI) datasets for assessing irradiation effects on normal liver tissue, edema, and hepatocyte dysfunction, obtained 6 and 12 weeks after HDR-BT, were merged with 3D dosimetry data. The isodose of the treatment plan covering the same volume as the irradiation effect was taken as a surrogate for the liver tissue tolerance dose. Catheter positioning accuracy was assessed by calculating the shift between the 3D center coordinates of the irradiation effect volume and the tolerance dose volume for 38 irradiation effects in 30 patients induced by catheters implanted in nearly parallel arrangement. Effects of prolonged irradiation were assessed in areas where the irradiation effect volume and tolerance dose volume did not overlap (mismatch areas) by using a catheter contribution index. This index was calculated for 48 irradiation effects induced by at least two catheters in 44 patients. Results Positioning accuracy of the brachytherapy catheters was 5-6 mm. The orthogonal and axial shifts between the center coordinates of the irradiation effect volume and the tolerance dose volume in relation to the direction vector of catheter implantation were highly correlated and in first approximation identically in the T1-w and T2-w MRI sequences (p = 0.003 and p < 0.001, respectively), as were the shifts between 6 and 12 weeks examinations (p = 0.001 and p = 0.004, respectively). There was a significant shift of the irradiation effect towards the catheter entry site compared with the planned dose distribution (p < 0.005). Prolonged treatment time increases the normal tissue tolerance dose. Here, the catheter contribution indices indicated a lower tolerance dose of the liver parenchyma in areas with prolonged irradiation (p < 0.005). Conclusions Positioning accuracy of brachytherapy catheters is sufficient for clinical practice. Reduced tolerance dose in areas exposed to prolonged irradiation is contradictory to results published in the current literature. Effects of prolonged dose administration on the liver tolerance dose for treatment times of up to 60 minutes per HDR-BT session are not pronounced compared to effects of positioning accuracy of the brachytherapy catheters and are therefore of minor importance in treatment planning.

90Y-radioembolization (RE) is a promising technique for delivering high doses of radiation to liver tumors but may result in compromise of liver function. To gain further perspective, we evaluated the toxicity rates of sequential lobar versus “whole liver” 90Y-radioembolization. Thirty-four patients with liver malignancy in noncirrhotic livers were included; 90Y-radioembolization was performed as either whole liver or sequential lobar treatment in 17 patients each. Standard clinical and liver specific laboratory parameters as well as MR imaging before treatment and at follow-up (6 and 12 weeks) after radioembolization were evaluated for toxicity using the Common Terminology Criteria for Adverse Events (CTCAE). Volumetry of the liver, tumor, and spleen and measurement of portal vein diameter also were performed. Three months after whole liver RE, 14 liver-related grade 3/4 events were recorded versus 2 events after sequential lobar treatment (P

We describe our initial clinical experience in artificial embolization with the Amplatzer Vascular Plug IV (VP IV), a further development of the Vascular Plug family already in routine use. Results from 50 embolization procedures conducted with the VP IV in 44 patients are summarized. All 50 embolizations were successful, although two required the technique to be modified because of problems with jamming of the screw thread and thus with disconnection of the plug. This was associated with large branching angles. With experience, the VP IV can be used safely and effectively, and it expands the spectrum of possible embolizations in interventional radiology. Its greatest disadvantage is its relatively poor positional controllability.