R. Straub

Liver metastases: interventional therapeutic techniques and results, state of the art.

Abstract. The liver is the most common site of metastatic tumour deposits. Hepatic metastases are the major cause of morbidity and mortality in patients with gastrointestinal carcinomas and other malignant tumours. The rationale and results for interventional therapeutic techniques in the treatment of liver metastases are presented. For the treatment of patients with irresectable liver metastases, alternative local ablative therapeutic modalities have been developed. Technique and results of local interventional therapies are presented such as microwave-, radiofrequency (RF)- and ultrasound ablation, and laser-induced interstitial therapy (LITT), cryotherapy and local drug administration such as alcohol injection, endotumoral chemotherapy and regional chemoembolisation. In addition to cryotherapy, all ablative techniques can be performed percutaneously with low morbidity and mortality. Cryotherapy is an effective and precise technique for inducing tumour necrosis, but it is currently performed via laparotomy. Percutaneous local alcohol injection results in an inhomogeneous distribution in liver metastases with unreliable control rates. Local chemotherapeutic drug instillation and regional chemoembolisation produces relevant but non-reproducible lesions. Laser-induced interstitial thermotherapy (LITT) performed under MRI guidance results in precise and reproducible areas of induced necrosis with a local control of 94 %, and with an improved survival rate. Interventional therapeutic techniques of liver metastases do result in a remarkable local tumour control rate with improved survival results.

Percutaneous MRI-guided laser-induced thermotherapy for hepatic metastases for colorectal cancer

procedure. LITT was done after agreement from the local ethics committee and with the patients’ informed consent. All patients tolerated the procedure well; six had mild nausea and a symptomless right subphrenic haemorrhage developed in one. No deaths, infections, or liver or bile-duct injury occurred. During follow-up, 23 of 99 treated patients died: one of myocardial infarction, one from a stroke, 13 from tumour progression in the liver, and eight from tumour progression in other locations. The cumulative survival rate was 0·88 after 12 months, 0·70 after 24 months, and 0·42 after 36 months. Median survival time, calculated by the Kaplan-Meier method, was 36·4 months (figure). In patients with liver metastases of colorectal cancer, local tumour destruction with LITT under local anaesthesia is well tolerated and results in improved clinical outcome and survival. Our data can be a basis for a randomised comparison of LITT versus surgery.

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.

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.

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.

Thermische Ablation von Lebermetastasen: Aktueller Stand und Perspektiven

ZusammenfassungZielsetzung. Vorstellung der thermischen Ablation von Lebermetastasen mittels laserinduzierter Thermotherapie (LITT). Material und Methodik. Verschiedene technische Verfahren der Ablation sowie “Online-monitoring-Verfahren” werden vorgestellt. Derzeit gängige Verfahren der Thermoablation stellen die MR-gesteuerte laserinduzierte Thermotherapie (LITT) sowie die Radiofrequenzablation (RF) dar. Ergebnisse. Im Rahmen einer prospektiven, nichtrandomisierten Studie wurden bislang 606 Patienten mit Lebermetastasen unterschiedlicher Primärtumoren mittels LITT perkutan therapiert. Die erzielte lokale Tumorkontrolle in der 3- bzw. 6-Monatskontrolle betrug dabei 98,3%, die Rate klinisch nicht relevanter Komplikationen 3,5%, die Rate klinisch relevanter Komplikationen 1,2%. Die mittlere Überlebensrate für das Gesamtkollektiv betrug 40,9 Monate. Es ergaben sich keine statistisch signifikanten Unterschiede der Überlebensraten für das kolorektale Karzinom, das Mammakarzinom sowie hinsichtlich weiterer Primärtumoren. Zur klinischen Relevanz der Radiofrequenzablation liegen derzeit nur Ergebnisse an kleinen Fallzahlen bei hoher Lokalrezidivrate vor. Schlussfolgerung. Das derzeit am besten evaluierte Therapieverfahren von Lebermetastasen stellt die MR-gesteuerte LITT aufgrund des optimalen Therapiemonitorings und der optimierten Interventionsmöglichkeiten dar.AbstractPurpose. To present thermal ablation of liver metastases via laser induced thermotherapy. Material and methods. Different technical procedures of thermal ablation and online monitoring are used, as there are the MR-guided laser induced thermotherapy (LITT) and the radiofrequency ablaton thermotherapy (RF). Results. In a prospective non randomized study 606 patients with liver metastases were treated via MR-guided laserinduced thermotherapy. Inclusion criteria were the exclusion of extrahepatic tumor spread and a number of metastases lower than 5 and a size lower than 50 mm in diameter. The local tumor control rate in the 3 month and 6 month control study was 98.3%, the complication rate 3,5% (clinically relevant: 1,2%). The mean survival rate was 40,9 months for all patients with liver metastases without statistically relevant differences for various primaries, like colorectal carcinoma, breast cancer and various other tumors. Results for radiofrequency are so far limited with incidence of a higher local tumor recurrence rate versus LITT. Conclusion. MR-guided LITT results in a high local tumor control rate with improved survival.

Oligonoduläres hepatozelluläres Karzinom (HCC): MR-gesteuerte laserinduzierte Thermotherapie (LITT)

ZusammenfassungZielsetzung. Evaluierung des therapeutischen Potenzials der MR-gesteuerten Thermotherapie (LITT) bei Patienten mit oligonodulärem hepatozellulärem Karzinom. Material und Methoden. 39 Patienten mit 61 intrahepatischen Läsionen wurden mittels der LITT therapiert. Dabei wurden ein Nd:YAG-Laser (1064 nm) und spezielle Power-Laser-Applikationssysteme perkutan eingesetzt. Qualitative und quantitative Parameter und klinische Daten wurden evaluiert. Ergebnisse. Alle 39 Patienten tolerierten die Therapie unter Lokalanästhesie, ohne dass klinisch relevante Komplikationen beobachtet wurden. Unter Einsatz spezieller Thermosequenzen konnte die MR-Tomographie als Onlinemonitoring eingesetzt werden. Bei Läsionen bis zu 2 cm wird mit einem Monoapplikator therapiert, bei größeren Läsionen wurde eine Multiapplikationstechnik eingesetzt. In 97,5% wurde eine komplette Nekrose induziert mit einem 5-mm-Sicherheitssaum ohne Lokalrezidiv in den Nachkontrollen. Die mittlere Überlebenszeit bei Patienten mit hepatozellulärem Karzinom lag bei 4,4 Jahren (95%-Konfidenzintervall 3,6–5,2 Jahre, Kaplan-Meier-Methode). Schlussfolgerungen. Die perkutane MR-gesteuerte LITT erlaubt eine hohe Tumorortskontrolle bei oligonodulären HCC-Läsionen mit einer Verbesserung der Überlebensdaten.AbstractPurpose. To prospectively evaluate the therapeutic potential of MR-guided laser-induced thermotherapy (LITT) in patients with oligonodular hepatocellular carcinoma. Material and methods. 39 patients with 61 intrahepatic lesions were treated with LITT. The Nd:YAG laser fiber was introduced with a percutaneously positioned irrigated laser application system. Qualitative and quantitative MR parameters and clinical data were evaluated. Results. All patients tolerated the procedure well under local anesthesia. All observed complications were minor and no further treatment was necessary. Online MR thermometry allowed exact visualization. Lesions up to 2 cm in diameter could be efficiently treated with a single laser application, larger lesions were treated simultaneous multiapplication. In 97.5% 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 was 4.4 years (95% CI: 3.6–5.2 years) after the time of diagnoses of the HCC (Kaplan-Meier-method). Conclusion. In intrahepatic oligonodular involvement of hepatocellular carcinoma LITT appears to be an effective therapeutic procedure with a high tumor contol rate and better survival data.

MR-Guided Laser-Induced Thermotherapy of the Infratemporal Fossa and Orbit in Malignant Chondrosarcoma via a Modified Technique

AbstractA 76-year-old patient presented with a recurrent mass of a malignant chondrosarcoma in the right infratemporal fossa and in the left maxillary sinus with orbital invasion. The patient was treated with a palliative intention with MR-guided laser-induced thermotherapy using a modified applicator technique. Following treatment clinical symptoms improved and MRI revealed complete laser-induced tumor necrosis.

Interventionelle MR-gesteuerte laserinduzierte Thermotherapie bei onkologischen Fragestellungen Stand und Ausblick

ZusammenfassungDie interventionelle MR-gesteuerte laserinduzierte Thermotherapie (LITT) wird derzeit klinisch und im Rahmen prospektiver Studien bei unterschiedlichen onkologischen Fragestellungen eingesetzt und evaluiert. Per definitionem stellt die MR-gesteuerte laserinduzierte Thermotherapie ein minimalinvasives Therapieverfahren dar, das auf der Laserwirkung mit resultierendem koagulativen Effekt beruht. Der thermoablative Effekt wird dabei „online”überwacht und dokumentiert durch den Einsatz spezieller MR-Sequenzprotokolle. Innerhalb eines Zeitraums von 6 Jahren wurden dabei prospektiv 335 Patienten mit malignen Weichteiltumoren therapiert und die Tumorortskontrollrate, die Komplikationsrate sowie die Überlebensdaten evaluiert. Die gewonnenen Ergebnisse zeigen, daß die MR-gesteuerte LITT ein nebenwirkungsarmes Therapieverfahren darstellt, mit einer enorm hohen Präzision und einer Tumorortskontrollrate bei optimierter Technik von >95%. Als Indikationen werden vorgestellt die Thermotherapie von primären und sekundären Lebermalignomen, sekundärer Lymphknoteninvasionen, abdomineller Rezidivtumoren sowie Tumorfragestellungen in der Kopf-/Halsregion.SummaryMR-guided LITT (laser-induced thermotherapy) is currently being evaluated for its effectiveness in clinical oncology. MR-guided LITT is defined as a minimally invasive technology based on the effects of the applied Nd-YAG laser on tumorous tissue. Due to specific characteristics of the laser-induced coagulative effect, online monitoring via MR thermometry is possible and extremely precise. In a period of 6 years 335 patients suffering from malignant soft tissue tumors were prospectively treated via MR-guided LITT. We evaluated the local tumor control rate, the rate of complications and the survival data from the clinical and MRI follow-up. Our results prove that MR-guided LITT results in a extremely low rate of side effects and an effective tumor control rate higher than 95%, depending on the size of the lesion. It is concluded that this therapeutic concept is of clinical value for patients with primary and secondary liver cancer, malignant lymph node involvement, abdominal recurrent tumors and tumors of the head and neck.

Therapiemöglichkeiten bei nicht resektablen LebermetastasenPercutane radiologische Interventionen

Summary. In patients with irresectable liver metastases the following spectrum of oncological concepts is in use. Percutaneous interventional methods allows for an optimized local control rate in strictly intrahepatic disease. Regional short-term time chemotherapy and transarterial chemoembolization (TACE) belong to regional methods. As local ablative methods, intratumoral drug application, endotumoral chemotherapy and alcohol instillation can be used. The most promising thermotherapeutic strategies are radiofrequency and laser-induced thermotherapy (LITT). In a prospective study 278 patients suffering from liver metastases were treated with MR-guided LITT and exact data for the local control rate and survival rate were evaluated. The overall cumulative survival rate (Kaplan-Meier) of patients with liver metastases was 40.8 months (median: 40.97 months, 95 % confidence interval 36.3–45.2).Zusammenfassung. Bei Patienten mit nicht resektablen Lebermetastasen müssen auf der Basis kurativer oder palliativer Therapiestrategien differenzierte onkologische Konzepte zum Einsatz kommen. Percutane interventionelle Verfahren erlauben eine Optimierung der lokalen Kontrollrate bei strikt intrahepatischen Prozessen. Zu den regionalen Verfahren zählen die lokal regionale Kurzzeitchemotherapie und die transarterielle Chemoembolisation (TACE). An lokal ablativen Verfahren werden einmal die lokale Medikamentenapplikation wie die endotumorale Chemotherapie und die Alkoholinstillation zusammengefaßt. Zu den vielversprechenden Thermotherapieverfahren zählen die Radiofrequenztherapie und die laserinduzierte Thermotherapie (LITT). Unter MR-Steuerung wurden in einer prospektiven Studie bislang 278 Patienten mit nicht resektablen Lebermetastasen therapiert. Die lokale Tumorkontrollrate lag hier bei 92 %, die kumulative Überlebensrate bei 40,8 Monate (Median: 40,97 Monate, 95 %-Konfidenzintervall 36,3–45,2).