Ricarda Rühl

Planning transarterial radioembolization of colorectal liver metastases with Yttrium 90 microspheres: evaluation of a sequential diagnostic approach using radiologic and nuclear medicine imaging techniques

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.

CT-Guided Interstitial Brachytherapy of Primary and Secondary Lung Malignancies

Background and Purpose:CT-guided interstitial brachytherapy of primary lung malignancies and pulmonary metastases represents a novel interventional technique, combining conventional high-dose-rate (HDR) iridium-192 (192Ir) brachytherapy with modern CT guidance for applicator positioning and computer-aided 3-D radiation treatment planning. The purpose of this study was to assess safety and efficacy of this technique.Patients and Methods:30 patients with 83 primary or secondary lung malignancies were recruited in a prospective nonrandomized trial (Table 1). After catheter positioning under CT fluoroscopy, a spiral CT was acquired for treatment planning (Figure 1). All but two patients received a defined single dose (coverage > 99%) of at least 20 Gy from a 192Ir source in HDR technique.Results:Adverse effects were nausea (n = 3, 6%), minor (n = 6, 12%) and one major pneumothorax (2%). Post intervention, no changes of vital capacity and forced expiratory volume could be detected. The median follow-up period was 9 months (1–21 months) with a local tumor control of 91% at 12 months (Figure 2).Conclusion:CT-guided interstitial brachytherapy proved to be safe and effective for the treatment of primary and secondary lung malignancies.Hintergrund und Ziel:Die CT-gesteuerte interstitielle Brachytherapie von primären Lungenmalignomen und Lungenmetastasen stellt eine weiterentwickelte interventionelle Technik dar, welche die konventionelle Hochdosisraten-(HDR)-Iridium-192-(192Ir-)Brachytherapie mittels moderner CT-Bildführung zur Applikatorpositionierung und computergestützter 3-D-Bestrahlungsplanung kombiniert. Ziel der Studie war die Analyse von Sicherheit und Effektivität dieses Verfahrens.Patienten und Methodik:30 Patienten mit 83 primären Lungenmalignomen oder pulmonalen Metastasen wurden in einer prospektiven, nicht randomisierten Phase-II-Studie behandelt (Tabelle 1). Nach Katheterpositionierung unter CT-Fluoroskopie erfolgte die Gewinnung eines 3-D-Datensatzes für die Bestrahlungsplanung (Abbildung 1). Alle Patienten bis auf zwei erhielten eine vorgeschriebene Einzeldosis (Abdeckung > 99%) von mindestens 20 Gy über eine 192Ir-Quelle in HDR-Technik.Ergebnisse:Minorkomplikationen waren Übelkeit (n = 3, 6%), diskreter (n = 6, 12%) sowie ein therapiebedürftiger Pneumothorax (2%). Postinterventionell ergaben sich keine Änderungen der Vitalkapazität oder des forcierten exspiratorischen Volumens. Die mediane Nachbeobachtungszeit betrug 9 Monate (1–21 Monate). Die lokale Tumorkontrolle lag nach 12 Monaten bei 91% (Abbildung 2).Schlussfolgerung:Die CT-gesteuerte interstitielle HDR-Brachytherapie stellt ein sicheres und effektives Verfahren zur Behandlung von primären Lungenmalignomen und pulmonalen Metastasen dar.

Radiobiological restrictions and tolerance doses of repeated single-fraction hdr-irradiation of intersecting small liver volumes for recurrent hepatic metastases.

BackgroundTo 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.MethodsTwenty 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.ResultsThe 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 pseudolesions 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.ConclusionsInactivation 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.

CT-guided brachytherapy (CTGB) versus interstitial laser ablation (ILT) of colorectal liver metastases: an intraindividual matched-pair analysis.

Purpose:To compare local tumor control after percutaneous tumor ablation by interstitial laser therapy (ILT) or CT-guided brachytherapy (CTGB).Patients and Methods: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.Results: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).Conclusion:CTGB demonstrated superior local tumor control compared to ILT in long-term follow-up.Ziel:Intraindividueller Vergleich lokaler Kontrollraten nach perkutaner Tumorablation mit interstitieller Lasertherapie (ILT) oder CT-gestützter Brachytherapie (CTGB) von intrahepatischen Metastasen bei kolorektalem Karzinom.Patienten und Methodik:Eine Matched-Pair-Analyse wurde bei 18 Patienten mit insgesamt 36 Lebermetastasen eines kolorektalen Karzinoms durchgeführt. Je eine Metastase wurde mit perkutaner Tumorablation mit ILT und je eine mit CTGB behandelt. Bei den Patienten mit identischer Tumorhistologie wurden folgende Faktoren betrachtet: 1. Tumorgröße ≤ 5 cm und 2. Durchführung oder Verzicht auf eine adjuvante Chemotherapie. Als primärer Endpunkt wurde die lokale Tumorkontrolle definiert.Ergebnisse:Die Verteilung der Tumorgrößen war gleich, und alle Patienten erreichten volle Übereinstimmung bis auf den Vergleichsfaktor der adjuvanten Chemotherapie. Die mediane Beobachtungszeit betrug 14 Monate (3–24 Monate) für beide Gruppen. Fünf von 18 Patienten (28%) hatten eine lokale Tumorprogression nach CTGB und zehn von 18 Patienten (56%) nach ILT. Die Differenz zwischen den Gruppen war für alle Patienten signifikant (p = 0,04). Bei der Betrachtung der Patienten mit völliger Übereinstimmung wurde die Signifikanzgrenze nicht erreicht (p = 0,23).Schlussfolgerung:Die CTGB zeigt in der Langzeitbeobachtung überlegene lokale Tumorkontrollraten im Vergleich zur ILT.

CT-Guided Brachytherapy (CTGB) versus Interstitial Laser Ablation (ILT) of Colorectal Liver Metastases

Purpose:To compare local tumor control after percutaneous tumor ablation by interstitial laser therapy (ILT) or CT-guided brachytherapy (CTGB).Patients and Methods: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.Results: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).Conclusion:CTGB demonstrated superior local tumor control compared to ILT in long-term follow-up.Ziel:Intraindividueller Vergleich lokaler Kontrollraten nach perkutaner Tumorablation mit interstitieller Lasertherapie (ILT) oder CT-gestützter Brachytherapie (CTGB) von intrahepatischen Metastasen bei kolorektalem Karzinom.Patienten und Methodik:Eine Matched-Pair-Analyse wurde bei 18 Patienten mit insgesamt 36 Lebermetastasen eines kolorektalen Karzinoms durchgeführt. Je eine Metastase wurde mit perkutaner Tumorablation mit ILT und je eine mit CTGB behandelt. Bei den Patienten mit identischer Tumorhistologie wurden folgende Faktoren betrachtet: 1. Tumorgröße ≤ 5 cm und 2. Durchführung oder Verzicht auf eine adjuvante Chemotherapie. Als primärer Endpunkt wurde die lokale Tumorkontrolle definiert.Ergebnisse:Die Verteilung der Tumorgrößen war gleich, und alle Patienten erreichten volle Übereinstimmung bis auf den Vergleichsfaktor der adjuvanten Chemotherapie. Die mediane Beobachtungszeit betrug 14 Monate (3–24 Monate) für beide Gruppen. Fünf von 18 Patienten (28%) hatten eine lokale Tumorprogression nach CTGB und zehn von 18 Patienten (56%) nach ILT. Die Differenz zwischen den Gruppen war für alle Patienten signifikant (p = 0,04). Bei der Betrachtung der Patienten mit völliger Übereinstimmung wurde die Signifikanzgrenze nicht erreicht (p = 0,23).Schlussfolgerung:Die CTGB zeigt in der Langzeitbeobachtung überlegene lokale Tumorkontrollraten im Vergleich zur ILT.

Sorafenib Therapy in Patients with Advanced Hepatocellular Carcinoma in Advanced Liver Cirrhosis

Background and Aim: Sorafenib has become the treatment standard for patients with advanced hepatocellular carcinoma (HCC). It is not clear whether patients with advanced liver function impairment (Child B) and patients undergoing additional locoregional therapy may tolerate treatment with sorafenib and benefit. We aimed to evaluate the tolerability and efficiency of sorafenib in patients with advanced HCC and different stages of liver cirrhosis, and in combination with locoregional therapy. Methods: In 50 patients with advanced HCC treated with sorafenib tolerability and efficiency of the therapy with respect to stage of liver cirrhosis, existence of extrahepatic tumor spread, and additional locoregional therapy were evaluated. Results: Fifty patients with advanced HCC were treated with sorafenib, and 13 received additional locoregional therapy. Tolerability of the systemic treatment was moderate in all patients, with no significant differences between the subgroups, while the median survival was better in patients with Child A than Child B cirrhosis. Conclusion: Tolerability and toxicity of a systemic treatment with sorafenib are moderate in patients with liver cirrhosis in Child A or B. Prospective randomized studies are required to evaluate the efficacy and tolerability of combined systemic and locoregional treatment approaches in patients with advanced HCC.

Assessment of Local Control after Laser-Induced Thermotherapy of Liver Metastases from Colorectal Cancer: Contribution of FDG-PET in Patients with Clinical Suspicion of Progressive Disease

Background: Management of patients after locally ablative treatment of liver metastases requires exact information about local control and systemic disease status. To fulfill these requirements, whole-body imaging using positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET) is a promising alternative to morphologic imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI). Purpose: To evaluate FDG-PET for the assessment of local control and systemic disease in patients with clinical suspicion of tumor progression after laser-induced thermotherapy (LITT) of colorectal liver metastases. Material and Methods: In 21 patients with suspicion of progressive disease after LITT, whole-body FDG-PET was performed. The presence of viable tumor within treated lesions, new liver metastases, and extrahepatic disease was evaluated visually and semiquantitatively (maximal standard uptake value [SUVmax], tumor-to-normal ratio [T/N]). The standard of reference was histopathology (n = 25 lesions) and/or clinical follow-up (>12 months) including contrast-enhanced MRI of the liver. Results: Among 54 metastases treated with LITT, 29 had residual tumor. Receiver operating characteristic (ROC) analysis of SUVmax (area under the curve (AUC) 0.990) and T/N (AUC 0.968) showed a significant discrimination level of negative or positive lesion status with an equal accuracy of 94% (51/54). The overall accuracy of visual FDG-PET was 96% (52/54), with one false-negative lesion among six examined within 3 days after LITT, and one false-positive lesion examined 54 days after LITT. In the detection of new intra- and extrahepatic lesions, FDG-PET resulted in correct alteration of treatment strategy in 43% of patients (P = 0.007). Conclusion: FDG-PET is a promising tool for the assessment of local control and whole-body restaging in patients with clinical suspicion of tumor progression after locally ablative treatment of colorectal liver metastases with LITT.

Hepatocellular Carcinoma and Liver Cirrhosis: Assessment of the Liver Function after Yttrium-90 Radioembolization with Resin Microspheres or after CT-Guided High-Dose-Rate Brachytherapy

Purpose: To identify changes of liver function after single-fraction irradiation or yttrium-90 radioembolization (90Y-RE) of hepatocellular carcinoma associated with liver cirrhosis on the basis of laboratory data. Methods and Materials: 24 patients with primary liver carcinoma and liver cirrhosis classified Child-Pugh A or B were treated either by image-guided high-dose-rate brachytherapy (HDR-BT) (12 patients) or by 90Y-RE (12 patients). The following laboratory parameters were assessed 1 day before and 3 days, 6 weeks and 3 months after the intervention: total bilirubin and γ-glutamyl transpeptidase (GGTP) as parameters of detoxification function, albumin and cholinesterase (ChE) as direct synthesis parameters, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (AP) as indicators of liver tissue damage. Preinterventional values were taken as baseline, following values were calculated as percentage changes from the baseline value. Statistical analysis was performed using the Wilcoxon-matched pairs test, comparing postinterventional with preinterventional values. Differences were considered statistically significant with a p value <0.05. Results: In all patients the median bilirubin, ALT, AP and albumin values remained within normal limits at any time of follow-up. AST levels in the RE group and GGTP in both groups have been already elevated over a normal range before the intervention, and in both groups both parameters showed a slight increase after interventions. ChE activity was lowered already in the baseline values and showed a further decrease 3 days after BT as well as 3 days and 6 weeks after RE, with final reconstitution to baseline values. All liver function test parameters showed mild changes shortly after radiation therapy but floating laboratory values recovering within 12 weeks to baseline values. Radiation or RE-induced liver disease was recorded in no patient. Conclusions: Liver function parameters show only mild changes shortly after intervention with recovery within 6–12 weeks to baseline values.

Image-Guided Interstitial High-Dose-Rate Brachytherapy in Hepatocellular Carcinoma

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.

Value of Combined PET/CT for Radiation Planning in CT-Guided Percutaneous Interstitial High-Dose-Rate Single-Fraction Brachytherapy for Colorectal Liver Metastases

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.