Katrin Eichler

Liver metastases of neuroendocrine carcinomas: Interventional treatment via transarterial embolization, chemoembolization and thermal ablation

UNLABELLED The aim of this review article is to provide a practical clinical guideline for indication, technical aspects, protocol guideline and strategies for the interventional treatment of liver metastases from neuroendocrine tumors and focusing on the results of various protocols of management. The response to therapy, in the published articles, is calculated on the basis of the following clinical parameters; including symptomatic response (SR), biologic response (BR), morphological response (MR), progress free survival (PFS), and survival periods (SP). Transarterial chemoembolization (TACE) has been associated with SR rates of 60-95%, BR of 50-90%, MR of 33-80%, SR of 20-80 months, and a 5-year survival of between 50% and 65%. PFS was also between 18 and 24 months. In the transarterial embolization (TAE) group, SR was similar to the TACE group, MR was 32% and 82%, survival was between 18 and 88 months with a survival rate of 40-67%, and BR was between 50% and 69%. Radiofrequency ablation (RFA), either percutaneous or during surgery, has been associated with SR of 71-95% for a mean duration of 8-10 months, BR of 65%, and mean SP of 1.6 years after ablation. The mean survival following surgical resection for operable cases is 4.26 years+/-S.D.: 1.1. CONCLUSION The interventional protocols for the management of liver metastases from neuroendocrine tumors: for oligonodular liver metastatic deposits, local resection or RFA and/or LITT is recommended, while in multinodular diseases with higher tumor load, TACE or TAE is recommended.

Laser-induced thermotherapy of malignant liver tumors: general principals, equipment(s), procedure(s) - side effects, complications and results

PURPOSE To prospectively evaluate the therapeutic potential of MR-guided and ultrasound-guided laser-induced thermotherapy (LITT) in patients with liver metastases and oligonodular hepatocellular carcinoma (HCC). MATERIAL AND METHODS Between June 1993 and June 2000 a total of 1608 LITT sessions was performed to treat 1914 lesions in 676 consecutive patients. The Nd-YAG laser fiber was introduced with a percutaneously positioned cooled application set. Qualitative and quantitative ultrasound and magnetic resonance (MR) parameters, as well as clinical data were evaluated. RESULTS All patients tolerated the procedure well under local anesthesia; no relevant clinical complications were observed. The mean laser power was 25 W and the mean duration was 25 min. MR proved to be superior over computed tomography and ultrasound due the thermosensitivity of the MR sequences allowing a better visualization of the volume of laser-induced changes and their relation to the neighboring geographical structures. The ultrasound-guided LITT should be restricted for patients with contraindications for MR imaging monitoring and for selected patients with low diameter oligonodular HCC. In 95% of cases, we achieved a complete necrosis of the tumor and a 5-mm safety margin, resulting in a complete destruction of the tumor without local recurrences. Mean survival in this group was 35 months (calculated with the Kaplan-Meier method). CONCLUSION MR-guided, or ultrasound-guided, LITT appears to be a safe and effective treatment protocol for liver metastases and oligonodular HCC.

Repeated Transarterial Chemoembolization in the Treatment of Liver Metastases of Colorectal Cancer: Prospective Study

PURPOSE To evaluate local tumor control and survival data after transarterial chemoembolization with different drug combinations in the palliative treatment of liver metastases in patients with colorectal cancer. MATERIALS AND METHODS The study was approved by institutional review board, and informed consent was obtained from all patients included in the study. A total of 463 patients (mean age, 62.5 years; range, 34.7-88.1 years) with unresectable liver metastases of colorectal cancer that did not respond to systemic chemotherapy were repeatedly treated with chemoembolization in 4-week intervals. In total, 2441 chemoembolization procedures were performed (mean, 5.3 sessions per patient). Of 463 patients, 67.4% had multiple (five or more) metastases, 8% had one metastasis, 10.4% had two metastases, and 14.3% had three or four metastases. The local chemotherapy protocol consisted of mitomycin C alone (n = 243), mitomycin C with gemcitabine (n = 153), or mitomycin C with irinotecan (n = 67). Embolization was performed with lipiodol and starch microspheres for vessel occlusion. Tumor response was evaluated with magnetic resonance imaging. The change in tumor size was calculated and the response was evaluated according to the Response Evaluation Criteria in Solid Tumors. Survival rates from first diagnosis and from first chemoembolization session were calculated according to the Kaplan-Meier method. Follow-up imaging was performed until patient death. RESULTS Evaluation of local tumor control resulted in partial response (68 patients [14.7%]), stable disease (223 patients [48.2%]), and progressive disease (172 patients [37.1%]). The 1-year survival rate after chemoembolization was 62%, and the 2-year survival rate was 28%. Median survival from date of diagnosis of liver metastases was 38 months and from the start of chemoembolization treatment was 14 months. There was no statistically significant difference between the three treatment protocols. CONCLUSION Chemoembolization is a minimally invasive therapy option for palliative treatment of liver metastases in patients with colorectal cancer, with similar results among three chemoembolization protocols.

Interventional MR: interstitial therapy

Abstract. The rationale and results for interstitial therapies via interventional MRI in the treatment of tumors in various regions are presented. Different interstitial treatment techniques are presented based on varying technologies both for tumor ablation and treatment monitoring. Data are presented based on 335 patients, 29–84 years of age (mean age 59 years, 196 men and 139 women) with a total of 932 liver tumors, 16 head and neck tumors and 14 abdominal recurrent pelvic and lymphatic tumors. All lesions had been treated with MR-guided laser-induced interstitial thermotherapy (LITT) via 2516 laser applications and 1856 cannulations. Data in the literature are extremely varying depending on author experience, treatment technique, and the included patient material. In our patient material we were able to achieve a local tumor control of 96.7 % depending on the size of the tumorous lesion, the topographical relationship, and the applied laser parameters. The overall cumulative survival rate of patients with liver metastases was 45.74 months (median 40.97 months, 95 % confidence interval 31.42–50.52). The cumulative survival rate of the patient group with hepatic metastases of colorectal carcinoma was 42.71 months (median 39.33 months, 95 % confidence interval 33.26–45.37). In patients with head and neck tumors a relevant reduction in clinically relevant symptoms such as pain, swallowing disorders, or nervous compression was achieved in 11 of 15 patients treated with LITT. In 14 soft tissue tumors, such as pelvic tumor recurrence and lymph node metastases, a local tumor control was obtained in 68 % of lesions. Interstitial therapies under interventional MRI guidance, such as LITT, results in a high local tumor control with an improved survival rate.

MR-compatible Assistance System for Biopsy in a High-Field-Strength System: Initial Results in Patients with Suspicious Prostate Lesions

PURPOSE To examine the feasibility and safety of magnetic resonance (MR)-guided biopsy by using a transgluteal approach in patients with suspicious prostate lesions by using an MR-compatible robotic system and a 1.5-T MR system. MATERIALS AND METHODS The study was approved by the institutional review board of University Frankfurt, and informed consent was obtained from each patient. A total of 20 patients (age range, 57.8-71.9 years; mean age, 65.1 years) underwent biopsy in a closed-bore high-field-strength MR system. Biopsy was performed with an MR-compatible pneumatically driven robotic system. T1-weighted gradient-echo fast low-angle shot and T2-weighted true fast imaging with steady-state precession sequences were used to plan and guide the intervention with a transgluteal access on the external planning computer of the assistance system. The system calculated the trajectory and then moved the guiding arm to the insertion point. The cannula was advanced manually, and biopsies were performed with the coaxial technique by using a 15-gauge pencil tip needle. Intervention time, complications, and biopsy findings were documented. RESULTS The MR-compatible robotic system did not interfere with image quality, nor did MR imaging cause dysfunction of the robot. In one patient, the interventionist caused a fail-safe system shutdown. This was due to inadvertent displacement of the guiding arm during cannula insertion. This problem was solved by increasing the displacement threshold. Accurate coaxial cannula biopsy could be performed in all subsequent patients. Sufficient histopathologic assessment was performed in 19 patients. Insufficient material was retrieved in the patient who experienced fail-safe system shutdown. The median intervention time was 39 minutes (23-65 minutes). No procedure-related complications were observed. CONCLUSION Preliminary results indicate that MR-guided robot-assisted biopsy is feasible and can be performed safely with highly accurate cannula placement.

Interstitial photodynamic laser therapy in interventional oncology

Photodynamic therapy (PDT) is a well-investigated locoregional cancer treatment in which a systemically administered photosensitizer is activated locally by illuminating the diseased tissue with light of a suitable wavelength. PDT offers various treatment strategies in oncology, especially palliative ones. This article focuses on the development and evaluation of interstitial PDT for the treatment of solid tumors, particularly liver tumors. The PDT is mostly used for superficial and endoluminal lesions like skin or bladder malignancies and also more frequently applied for the treatment of lung, esophageal, and head and neck cancer. With the help of specially designed application systems, PDT is now becoming a practicable option for solid lesions, including those in parenchymal organs such as the liver. After intravenous treatment with the photosensitizer followed by interstitial light activation, contrast-enhanced computed tomography shows the development of therapy-induced necrosis around the light-guiding device. With the use of multiple devices, ablation of liver tumors seems to be possible, and no severe side effects or toxicities related to the treatment are reported. PDT can become a clinically relevant adjunct in the locoregional therapy strategies.

CT-guided intratumoural administration of cisplatin/epinephrine gel for treatment of malignant liver tumours

To analyze prospectively the interventional and clinical aspects of computed tomography-guided direct intratumoural injection of a novel chemotherapeutic administration and the parenchymal changes of tumour and necrosis in malignant liver tumours. Eight patients with 17 colorectal liver metastases were treated with a mean of 5.1 injections and nine patients with 13 hepatocellular carcinoma nodules with a mean of 3.1 treatments with computed tomography guided local applications of a novel cisplatin/epinephrine gel. This application provides a higher local and lower systemic drug concentration. Volumes of tumour and necrosis prior and after treatment were measured by computer generated volumetric analysis. Contrast enhanced studies verified pretherapeutic viable tumour volumes with a value of 77.4 ml in the metastases and 29.2 ml in the hepatocellular carcinoma nodules. Intratumoural drug application resulted in a significant increase of necrosis and a decrease in viable tumour volume to be 68.3 ml in metastases and 14.5 ml in hepatocellular carcinoma. Local therapy control rate for the follow up to 6 months was 38 and 71% for the group of metastases and hepatocellular carcinoma, respectively. Direct intratumoural injection of cisplatin/epinepthrine injectable gel is a feasible and good tolerated method and results in the development of a statistically significant increase in necrosis in malignant liver tumours. For hepatocellular carcinoma a higher local therapy control rate compared to colorectal metastases can be reported.

First human study in treatment of unresectable liver metastases from colorectal cancer with irinotecan-loaded beads (DEBIRI)

The objective of this pilot clinical study was to assess the safety, technical feasibility, pharmacokinetic (PK) profile and tumour response of DC Bead™ with irinotecan (DEBIRI™) delivered by intra-arterial embolisation for the treatment of metastatic colorectal cancer. Eleven patients with unresectable liver metastases from CRC, tumour burden <30% of liver volume, adequate haematological, liver and renal function, performance status of <2 were included in this study. Patients received up to 4 sessions of TACE with DEBIRI at 3-week intervals. Feasibility of the procedure, safety and tumour response were assessed after each cycle. PK was measured after the first cycle. Patients were followed up to 24 weeks. Only mild to moderate adverse events were observed. DEBIRI is a technically feasibile procedure; no technical complications were observed. Average Cmax for irinotecan and SN-38 was 194 ng/ml and 16.7 ng/ml, respectively, with average t½ of 4.6 h and 12.4 h following administration of DEBIRI. Best overall response during the study showed disease control in 9 patients (2 patients with partial response and 7 with stable disease, overall response rate of 18%). Our study shows that transarterial chemoembolisation with irinotecan-loaded DC beads (DEBIRI) is safe, technically feasible and effective with a good PK profile.

Volumetric evaluation of liver metastases after thermal ablation: long-term results following MR-guided laser-induced thermotherapy.

PURPOSE To volumetrically analyze liver metastases and posttherapeutic findings of the thermally ablated area after thermal ablation with magnetic resonance (MR)-guided laser-induced thermotherapy in a long-term evaluation using contrast-enhanced MR imaging. MATERIALS AND METHODS The study was approved by the institutional review board, and informed consent was obtained from all patients. In 40 patients (27 women, 13 men; age range, 33-94 years; mean age, 62.5 years) in whom colorectal cancer (n = 20) and breast cancer (n = 20) had metastasized to the liver, initial tumor volume and thermal-induced necrosis after MR-guided laser-induced thermotherapy were retrospectively analyzed. All patients presented with oligonodular liver metastases and underwent follow-up with contrast-enhanced MR imaging for at least 3 years. No concomitant oncologic therapies were performed. RESULTS Volumetric MR imaging evaluation depicted 40 metastases with an initial tumor volume less than 5 mL (x = 1.75), nine metastases with initial volume of 5-20 mL (x = 12.35), and eight metastases with initial volume more than 20 mL (x = 50.57). The mean volume of the thermally damaged area was 498% of the initial volume for colorectal cancer metastases and 604% of the initial volume for breast cancer metastases. The ischemic and necrotic volume for colorectal cancer metastases had decreased by a mean of 48.6% after 3 months, by 63% after 6 months, by 70.2% after 12 months, and by 92.2% after 36 months. For breast cancer metastases at 36 months, the necrotic volume had decreased by 80.61%; the reduction in the volume of the thermally damaged region was statistically significantly lower than that of colorectal cancer metastases. CONCLUSION MR-guided laser-induced thermotherapy induced a high volume of thermal ablation; the greatest reduction in the necrotic volume occurred in the first year, and lower values were seen in the next period. The reduction was statistically significantly higher in colorectal cancer metastases.

Radiation exposure to operating staff during rotational flat-panel angiography and C-arm cone beam computed tomography (CT) applications

PURPOSE To evaluate the radiation exposure for operating personnel associated with rotational flat-panel angiography and C-arm cone beam CT. MATERIALS AND METHODS Using a dedicated angiography-suite, 2D and 3D examinations of the liver were performed on a phantom to generate scattered radiation. Exposure was measured with a dosimeter at predefined heights (eye, thyroid, breast, gonads and knee) at the physicians location. Analysis included 3D procedures with a field of view (FOV) of 24 cm × 18 cm (8s/rotation, 20s/rotation and 5s/2 rotations), and 47 cm×18 cm (16s/2 rotations) and standard 2D angiography (10s, FOV 24 cm×18 cm). RESULTS Measurements showed the highest radiation dose at the eye and thyroid level. In comparison to 2D-DSA (3.9 μSv eye-exposure), the 3D procedures caused an increased radiation exposure both in standard FOV (8s/rotation: 28.0 μSv, 20s/rotation: 79.3 μSv, 5s/2 rotations: 32.5 μSv) and large FOV (37.6 μSv). Proportional distributions were measured for the residual heights. With the use of lead glass, irradiation of the eye lens was reduced to 0.2 μSv (2D DSA) and 10.6 μSv (3D technique with 20s/rotation). CONCLUSION Rotational flat-panel angiography and C-arm cone beam applications significantly increase radiation exposure to the attending operator in comparison to 2D angiography. Our study indicates that the physician should wear protective devices and leave the examination room when performing 3D examinations.