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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.

Purpose To determine the additional value of fluorodeoxyglucose-positron emission tomography (PET) for clinical target volume definition in the planning of computed tomography (CT)-guided interstitial brachytherapy for liver metastases. Patients and Methods A total of 19 patients with liver metastases from colorectal cancer treated in 25 sessions were included in the present study. All patients had undergone fluorodeoxyglucose-PET for patient evaluation before interstitial CT-guided brachytherapy. A contrast-enhanced CT scan of the upper abdomen was obtained for radiation planning. The clinical target volume (CTV) was defined by a radiation oncologist and radiologist. After registration of the CT scan with the PET data set, the target volume was defined again using the fusion images. Results PET revealed one additional liver lesion that was not visible on CT. The median CT-CTV (defined using CT and magnetic resonance imaging) was 68 cm 3 (range 4–260). The PET/CT-CTV (median, 78 cm 3 ; range, 4–273) was significantly larger, with a median gain of 24.5% (interquartile range, 2.1–71.5%; p = .022). An increased CTV was observed in 15 cases and a decrease in 6; in 4 cases, the CT-CTV and PET/CT-CTV were equal. Incomplete dose coverage of PET/CT-CTVs was indicative of early local progression ( p = .004); however, CT-based radiation plans did not show significant differences in the local control rates when stratified by dose coverage. Conclusion Retrospective implementation of fluorodeoxyglucose-PET for CTV specification for CT-guided brachytherapy for colorectal liver metastases revealed a significant change in the CTVs. Additional PET-positive tumor regions with incomplete dose coverage could explain unexpected early local progression.

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.

To assess both sensitivity and specificity of digital chest radiography alone and in conjunction with dual-exposure dual-energy chest radiography for the detection and classification of pulmonary nodules. One hundred patients with a total of 149 lung nodules (3-45 mm; median, 11 mm) confirmed by CT were included in this study. Dual-exposure dual-energy chest radiographies of each patient were obtained using a CsI detector system. Experienced board-certified chest radiologists from four different medical centers in Europe reviewed standard chest radiographs alone and in conjunction with dual-energy images blinded and in random order. The reviewers rated the probability of presence, calcification and malignancy of all lung nodules on a five-point rating scale. Lesions detected were identified by applying a specific coordinate system to enable precise verification by the study leader. A receiver-operating characteristic (ROC) analysis was performed. In addition to the 149 true-positive CT proven lesions, 236 false-positive lung nodules were described in digital chest radiographies in conjunction with dual-energy chest radiographies. The cumulative sensitivity of chest radiography in conjunction with dual energy was 43%, specificity was 55%. For digital radiography alone, sensitivity was 35% and specifity was 83%. For the dual energy system, positive predictive value was 58%, and negative predictive value was 66% compared to the digital radiography with a positive predictive value of 59% and a negative predictive value of 65%. Areas under the curve in a ROC analysis resulted in 0.631 (95% confidence interval =0.61 to 0.65) for radiography with dual energy and 0.602 (95% confidence interval =0.58 to 0.63) for digital radiography alone. This difference was not statistically significant. For the detection of lesion calcification or the determination of malignancy, ROC analysis also failed to show significant differences. CsI-based flat-panel dual-exposure dual-energy imaging added to standard chest radiography did not show statistically significant improvement for the detection of pulmonary nodules, nor the identification of calcifications, nor the determination of malignancy.

The purpose of the study was to establish a diagnostic approach to the preparation of patients with colorectal liver metastases considered for transarterial radioembolization (RE). Twenty-two patients sequentially underwent computed tomography (CT; thorax/abdomen), magnetic resonance imaging (MRI; liver; hepatocyte-specific contrast), positron emission tomography (PET/PET-CT; F18-fluoro-desoxy-glucose), and angiography with perfusion scintigraphy [planar imaging; tomography with integrated CT (SPECT-CT)]. The algorithm was continued when no contraindication or alternative treatment option was found. The impact of each test on the therapy decision and RE management was recorded. Patient evaluation using CT revealed contraindications for RE in 4/22 patients (18%). Of the remaining 18 patients, 2 were excluded and 3 were assigned to locally ablative treatment based on MRI and PET results (28%). The remaining 13 patients entered the planning algorithm: SPECT-CT revealed gastrointestinal tracer accumulations in 4 (31%) patients [SPECT, 2 (15%)], making a modified application necessary. In five patients (38%), planar scintigraphy revealed relevant hepatopulmonary shunting. Therapy was finally administered to all 13 patients without therapy-related pulmonary or gastrointestinal morbidity. Each part of the diagnostic algorithm showed a relevant impact on patient management. The sequential approach appears to be suitable and keeps the number of unnecessary treatments and therapy risks to a minimum.

Background To assess radiobiological restrictions and tolerance doses as well as other toxic effects derived from repeated applications of single-fraction high dose rate irradiation of small liver volumes in clinical practice. Methods Twenty patients with liver metastases were treated repeatedly (2 - 4 times) at identical or intersecting locations by CT-guided interstitial brachytherapy with varying time intervals. Magnetic resonance imaging using the hepatocyte selective contrast media Gd-BOPTA was performed before and after treatment to determine the volume of hepatocyte function loss (called pseudolesion), and the last acquired MRI data set was merged with the dose distributions of all administered brachytherapies. We calculated the BED (biologically equivalent dose for a single dose d = 2 Gy) for different α/β values (2, 3, 10, 20, 100) based on the linear-quadratic model and estimated the tolerance dose for liver parenchyma D90 as the BED exposing 90% of the pseudolesion in MRI. Results The tolerance doses D90 after repeated brachytherapy sessions were found between 22 - 24 Gy and proved only slightly dependent on α/β in the clinically relevant range of α/β = 2 - 10 Gy. Variance analysis showed a significant dependency of D90 with respect to the intervals between the first irradiation and the MRI control (p < 0.05), and to the number of interventions. In addition, we observed a significant inverse correlation (p = 0.037) between D90 and the pseudolesion's volume. No symptoms of liver dysfunction or other toxic effects such as abscess formation occurred during the follow-up time, neither acute nor on the long-term. Conclusions Inactivation of liver parenchyma occurs at a BED of approx. 22 - 24 Gy corresponding to a single dose of ~10 Gy (α/β ~ 5 Gy). This tolerance dose is consistent with the large potential to treat oligotopic and/or recurrent liver metastases by CT-guided HDR brachytherapy without radiation-induced liver disease (RILD). Repeated small volume irradiation may be applied safely within the limits of this study.

Backround Micrometastases of colorectal liver metastases are present in up to 50% of lesions. In this study we sought to determine the threshold dose for local control of occult micrometastases in patients undergoing CT (computed tomography)-guided brachytherapy of colorectal liver metastases. Materials and methods Nineteen patients demonstrated 34 local tumor recurrences originating from micrometastases after CT-guided brachytherapy of 27 colorectal liver metastases. We considered a local tumor recurrence as originating from a micrometastasis if tumor regrowth occurred adjacent to a formerly irradiated lesion and the distance of the 3D isocenter of the new lesion was ≤ 23.5 mm from the previous tumor margin. Follow-up MRI was fused with the planning-CT and dosimetry data. Two reviewers independently indicated the dose exposure at the isocenter of the micrometastases. Statistical analysis included an analysis of variance (ANOVA) using backward selection. 95% tolerance intervals with coverage of 87.5 and 75% of the data of the normal distribution were calculated. Results The median distance of the micrometastases to the margin of the originating colorectal metastases was 8.75 mm (1-21 mm). Dose exposure at the isocenter was 12.25 Gy (7-19.8) in median. We stratified according to the distance from the isocenter to the initial tumor margin: ≤ 9 mm, > 9-15 mm and > 15 mm. The median dose in the according isocenters was 13.18, 11.6 and 11.85 Gy. The threshold dose failing to prevent micrometastasis growth was sigificantly higher in a subgroup of lesions with ≤ 9 mm distance as compared to > 15 mm (13.18 vs 11.85 Gy). Adjuvant chemotherapy correlated with greater distance of micrometastasis growth to the tumor but not with the threshold dose. Conclusion To prevent loss of local tumor control by continuous growth of micrometastases a threshold dose of 15,4 Gy (single fraction) should be delivered at a distance of 21 mm to the gross tumor margin.

To prospectively evaluate diffusion-weighted imaging (DWI) for early prediction of tumour response in patients with colorectal liver metastases following selective internal radiotherapy (SIRT).We evaluated 41 metastases in 21 patients, age 62.9 ± 9.9 years. All patients underwent magnetic resonance imaging (MRI) including breath-hold echoplanar DWI sequences. Imaging was performed before therapy (baseline MRI), 2 days after SIRT (early MRI) as well as 6 weeks later (follow-up MRI). Tumour volume (TV) and intratumoural apparent diffusion coefficient (ADC) were measured independently by two radiologists at all time points.Metastases were categorised as responding lesions (RL; n = 33) or non-responding lesions (NRL; n = 8) according to changes in TV after 6 weeks. We found an inverse correlation of changes in TV and ADC at follow-up MRI with a Pearson's correlation coefficient of r = -0.66 (p 0.0001). On early MRI, no significant changes in TV were found for either RL or NRL. Conversely, ADC decreased significantly in RL by 10.7 ± 8.4% (p 0.0001). ADC increased in NRL by 9.6 ± 20.8%, which was not statistically significant (p = 0.40).DWI was capable of predicting therapy effects of SIRT in patients with colorectal hepatic metastases as early as 2 days following treatment.

This prospective study was designed to assess the diagnostic value of magnetic resonance angiography (MRA) with blood-pool contrast agent (gadofosveset) in the detection of type-II endoleak after endovascular aortic repair (EVAR).Thirty-two patients with aortic aneurysms who had undergone EVAR were included in this study. All patients were examined by dual-phase computed tomography angiography (CTA) as well as MRA with gadofosveset in the first-pass and steady-state phases. Two independent readers evaluated the images of CTA and MRA in terms of endoleak type II, feeding vessel, and image quality.Median follow-up-time after EVAR was 22 months (range 4 to 59). Endoleak type II was detected by CTA in 12 of 32 patients (37.5%); MRA detected endoleak in all of these patients as well as in another 9 patients (n = 21, 65.6%), of whom the endoleaks in 6 patients showed an increasing diameter. Most endoleaks were detected in the steady-state phase (n = 14). The decrease in diameter of the aneurysmal sac was significantly greater in the patients without a visible endoleak that was visible on MRA (P = 0.004). In the overall estimation of diagnostic accuracy, MRA was judged superior to CTA in 66% of all examinations.MRA with gadofosveset appeared superior to CTA, and has higher diagnostic accuracy, in the detection of endoleak after EVAR.

To prospectively assess a dose-response relationship for the hepatic reticulo-endothelial system (RES) after small volume single fraction irradiation of liver parenchyma in vivo.Twenty-five liver tumors were treated by computed tomography (CT)-guided interstitial brachytherapy. Magnetic resonance imaging (MRI) was performed 1 day before and 3 days, 6, 12 and 24 weeks after therapy. MR-sequences included T2-w Turbo Spin Echo (TSE) enhanced by hepatic RES targeted Standard Superparamagnetic Iron Oxide (SSPIO). All MRI data sets were merged with three dimensional (3D) dosimetry data and evaluated by two radiologists. We estimated the threshold dose for either edema or function loss as the D90. A match-pair analysis was performed with another 25 liver tumors, which were treated the same but had MRI follow-up using the hepatocyte specific MRI contrast media Gadobenate dimeglumine (Gd-BOPTA).Three days post brachytherapy the D90 for hepatic RES function loss reached the 18.3 Gray (Gy) isosurface (Standard Deviation (SD) 7.7). At 6 weeks, the respective zone had increased significantly to the 12.9 Gy isosurface (SD 4.4). After 12 and 24 weeks, the dysfunction of liver volume decreased significantly to the 15 Gy and 20.4 Gy isosurface respectively (SD 7.1 and 10.0). Comparison to the hepatocyte function loss indicates a higher minimal threshold dose of the hepatic RES.Hepatic RES demonstrated a high regenerative capacity and a higher minimal threshold dose than hepatocytes. Temporary function loss was found from the 13 Gy isosurface.

Ziele: MRT basierte volumetrische Evaluation der Effektivitat der „Selective Internal Radiation Therapy“ (SIRT) bei Patienten mit therapierefraktarer progredienter Lebermetastasierung bei kolorektalem Karzinom. Methode: In einer prospektiven Studie wurden 4 Patienten konsekutiv untersucht. Alle Patienten hatten eine chirurgisch nicht resektable, ausgedehnte hepatische Metastasierung. Die Behandlungsoptionen mit Chemotherapeutika und monoklonalen Antikorpern waren ausgeschopft. Vor der Behandlung mit der SIRT und 3 Monate nach der SIRT wurde eine MRT-Untersuchung an einem 1,5 Tesla Gerat mit leberspezifischem Kontrastmittel (Primovist®) durchgefuhrt. Angiographisch wurden pratherapeutisch die extrahepatischen Gefasaste der A. hepatica communis (A. gastroduodenalis, A. cystica und aberrante Gefasaste des Pankreas) embolisiert um eine Verschleppung der Partikel zu verhindern und nach intraarterieller Injektion von Tc-99m-MAA (160 MBq +/- 20) das Ausmas der intrahepatalen Shunts bestimmt. Anschliesend erfolgte die Applikation der Yttrium-90 markierten biokompatiblen Mikrospharen (1,6 GBq +/- 0,2) uber die A. hepatica communis. Die Volumina der Lebermetastasen wurden an einer Bildnachverarbeitungsworkstation manuell bestimmt. Die pra- und posttherapeutischen Volumina wurden miteinander verglichen. Ergebnis: Samtliche Patienten zeigten in den posttherapeutisch durchgefuhrten MRT-Kontrollen nach 3 Monaten eine Volumenreduktion der Lebermetastasen von insgesamt ca. 23% (19%-26%). Schlussfolgerung: Die SIRT ist eine sinnvolle Therapieoption bei hepatisch metastasiertem kolorektalem Karzinom. Korrespondierender Autor: Seemann MD Universitat Magdeburg, Radiologie und Nuklearmedizin, Leipziger Strasse 44, 39120 Magdeburg E-Mail: marcus.seemann@medizin.uni-magdeburg.de

Ziele: Ziel war die Evaluierung von Durchfuhrbarkeit, Sicherheit und Effektivitat verschiedener Kombinationstherapien von interstitieller Hochdodsis(HDR)- Brachytherapie und intraarterieller Chemotherapie der Leber bei Colon-CA-Metastasen Methode: In diese Studie wurden 33 Patienten (Alter: 28–77 Jahre) mit Lebermetastasen bei kolorektalem Karzinom eingeschlossen. Die Patienten wurden mit drei unterschiedlichen Kombinationen aus intraartieller Chemotherapie (HAI) uber ein intraarterielles Portsystem in der A. hepatica und HDR-Brachytherapie behandelt. Die Subgruppe A (n=15) wurde zuerst mit HAI behandelt und nach partieller Remission zusatzlich eine HDR-Brachytherapie der verbliebenen Tumoranteile durchgefuhrt. Die Patienten in der Subgruppe B (n=9) erhielten zuerst eine interstitielle Brachytherapie und direkt im Anschluss zusatzlich eine HAI. In der Subgruppe C (n=9) wurden initial mit HDR-Brachytherapie behandelt und erst bei erneutem Tumorwachstum, das fur lokal ablative Masnahmen nciht sinnvoll erschien, wurde eine HAI angeschlossen. Ergebnis: Der mittlere Tumordurchmesser der mit Brachytherapie behandelten Metastasen lag bei 4,6cm (1–12cm). Die mittlere tumorumschleisende Dosis betrug 18Gy (15–25Gy). Fruhe minor Komplikationen waren Schmerz (n=2) und Fieber (n=2). Major Komplikationen umfassten Pneumothorax (n=1), p.i. Blutung (n=1) und einen biliaren Abszess. Die durchschnittliche Anzahl behandelter Tumoren pro Intervention lag bei 2,3 (1–7) Fur die eingebrachten i.a. Portsysteme war die mittlere Verweildauer 297 Tage (17–740 Tage). Acht Patienten tolerierten die i.a. Chemotherapie ohne Nebenwirkungen. Gemas der WHO-Klassifikation traten bei 6 Patienten Grad I und bei 11 Patienten Grad II Nebenwirkungen auf. Bei 7 Patienten wurden WHO Grad III Nebenwirkungen und bei einem Grad IV Nebenwirkungen festgestellt Die mediane Follow-up Zeit fur alle 33 Patienten war 23 Monate (7–54 Monate). Gemas Kaplan-Meier-Methode lag das Overall-survival bei 100% nach 6 Monaten, bei 93,4% nach 12 Monaten, 89,7% nach 18 Monaten und 66,8% nach 24 Monaten. Die median lokale Tumorkontrolle der Metastasen nach Brachytherapie und HAI betragt zur Zeit 12,3 Monate (3–45 Monate) Schlussfolgerung: In dieser Studie konnte gezeigt werden, dass in der Behandlung von Patienten mit hepatisch metastasiertem Colon-CA Kombinationen aus zwei minimal invasiven Therapiemethoden HAI und HDR-Brachytherapie gut und sicher durchfuhrbar sind, bei gleichzeitig guten Uberlebenszeiten. Korrespondierender Autor: Wieners G Otto-von-Guericke Universitat Magdeburg, Klinik fur Radiologie und Nuklearmedizin, Leipzigerstr. 44, 39120 Magdeburg E-Mail: gero.wieners@medizin.uni-magdeburg.de

Ziele: Bestimmung der Wertigkeit der FDG-PET und PET-CT bei der Planung klinischer Zielvolumina (CTV) fur die CT-gestutzte Brachytherapie von kolorektalen Lebermetastasen und Erarbeitung eines Workflow fur die prospektive Anwendung. Methode: Bisher wurden 15 Patienten mit Lebermetastasen retrospektiv eingeschlossen. Alle Patienten hatten unmittelbar (max. 1 Tage) vor der Therapie eine Ganzkorper FDG-PET (PET n=x, PET-CT n=y) und eine Leber-MRT (hepatozytenspezifisches Kontrastmittel) fur Restaging und Evaluation. Fur die Therapie wurden zunachst CT-gestutzt Afterloading-Katheter perkutan in die Lebertumoren implantiert. Eine intravenous kontrastgestutzte CT mit implantierten Kathetern diente der Brachytherapie-Planung, wobei die CTVs mithilfe der MRT-Bilder auf der Planungs-CT definiert wurden um dann einen Bestrahlungsplan fur die Ir192-Quelle mit Haltepunkten und Verweilzeiten mit der Zielvorgabe einer Tumor umschliesenden Mindestdosis zu erstellen (jeweils ein Strahlentherapeut, Strahlenphysiker, Interventions-Radiologe und Nuklearmediziner im Konsensus, Workstation: Brachyvision). In einem zweiten Schritt, unabhangig von der tatsachlichen Therapie, wurden die CTVs, nach Fusion der Planungs-CT mit den importierten und segmentierten PET-Daten des Oberbauches, erneut definiert und statistisch mit den CT-CTVs verglichen. Ergebnis: Verglichen zur CT und MRT wurden bei keinem der 15 Patienten zusatzliche, zu therapierende Lebermetastasen durch die FDG-PET identifiziert. Die Fusion der FDG-PET mit der Planungs-Spiral-CT wurde in allen 15 Fallen als anatomisch korrekt bewertet. Das Volumen der CTVs, wie es in der Planungs-CT unter Berucksichtigung der MRT-Bildgebung geplant wurde betrug 19–478ml (Mittelwert 190ml (±156 SD)). Die CTVs vergroserten sich signifikant auf 27–603ml (Mittelwert 211ml (±180 SD)), wenn die Planung mithilfe der fusionierten PET-Daten erfolgte (p