Stereotactic body radiotherapy in patients with hepatocellular carcinoma in a multimodal treatment setting

  • Sabine Gerum
  • Christian Heinz
  • Claus Belka
  • Franziska Walter
  • Philipp Marius Paprottka
  • Enrico N De Toni
  • Falk RoederEmail author
Original Article



Retrospective evaluation of stereotactic body radiation therapy (SBRT) in patients with hepatocellular carcinoma (HCC).


We retrospectively analyzed 36 patients (45 lesions) treated between 2011 and 2017. Twenty-seven had previous treatments. Current treatment consisted of SBRT alone (n = 15) or selective transarterial chemoembolization (TACE) followed by SBRT to the same lesions (n = 21). Eight patients received additional local treatments to different lesions. Liver function was predominantly moderately restricted (Child A: 29, Child B: 6, Child C: 1). Treatment planning was based on 4D-computed tomography, dose/fractionation varied depending on location and size, most commonly 3 fractions of 12.5 Gy (65% isodose) and 5 fractions of 8 Gy (80% isodose).


Median follow-up was 15 months. Local recurrence was observed in 3 lesions (7%), resulting in 1‑and 2‑year local control rates of 93%. The only significantly predicting factor was the use of abdominal compression. New hepatic lesions occurred in 19 patients (52%), 1‑ and 2‑year freedom-from-hepatic-failure (FFHF) was 39% and 32%, respectively. Only the number of treated lesions was predictive for FFHF. Sixteen patients have died, resulting in 1‑ and 2‑year overall survival (OS) of 64% and 41%, respectively, significantly impacted by the number of treated lesions and Child–Pugh class. Severe acute and late toxicity (≥grade 3) was observed in 3% and 8%, respectively. 6 patients (17%) received liver transplantation (OLT) after SBRT, of whom 5 showed pathological complete remission.


SBRT (±TACE) in highly pretreated HCC is effective and associated with excellent LC and low toxicity. SBRT may be used as definitive or bridging treatment prior to OLT. Patients with multifocal lesions have significantly decreased 1‑ and 2‑year FFHF and OS.


Liver Hepatocellular carcinoma Stereotactic body radiation therapy Orthotopic liver transplantation Multimodal treatment 



four-dimensional computed tomography




Barcelona Clinical Liver Cancer


biologically effective dose


cone beam computed tomography


cubic centimeters

CP class

Child–Pugh class


computed tomography


Common Toxicity Criteria for Adverse Events


freedom from hepatic failure


gross tumor volume


hepatocellular carcinoma




intensity-modulated radiation therapy


internal target volume


Karnofsky performance score


local control


local recurrence


magnetic resonance imaging


orthotopic liver transplantation


overall survival


pathologic complete response


progression-free survival


pathologic partial response


planning target volume


radiofrequency ablation


radiation-induced liver disease


stereotactic body radiation therapy


selective internal radiotherapy


transarterial chemoembolization

Stereotaktische Bestrahlungstherapie bei Patienten mit hepatozellulärem Karzinom im Rahmen multimodaler Behandlung



Ziel war die retrospektive Evaluation der Bestrahlungstherapie mittels Körperstereotaxie (SBRT) beim hepatozellulären Karzinom (HCC).


Die retrospektive Analyse umfasst 36 Patienten (45 Läsionen), welche zwischen 2011 und 2017 behandelt wurden. Lokale Vorbehandlungen erhielten 27 Patienten. Aktuell wurden 15 Patienten mittels alleiniger SBRT und 21 mittels SBRT nach selektiver transarterieller Chemoembolisation (TACE) der gleichen Läsion behandelt. Bei 8 Patienten erfolgten zusätzlich lokale Behandlungen anderer Läsionen. Die Leberfunktion war überwiegend gering eingeschränkt (Child A: 29, Child B: 6, Child C: 1). Die Therapieplanung erfolgte mittels 4‑D-Computertomographie, die Dosis/Fraktionierung war abhängig von Lokalisation und Größe, üblicherweise 3 × 12,5 Gy (65%-Isodose) oder 5 × 8 Gy (80%-Isodose).


Die mediane Nachbeobachtungszeit betrug 15 Monate. Es traten 3 Lokalrezidive auf (7%) auf, die Ein-und 2‑Jahres-Lokalkontrollrate betrug 93%. Der einzige signifikante prädiktive Faktor war die Verwendung einer Bauchpresse. Bei insgesamt 19 Patienten (52%) traten neue hepatische Läsionen auf, das leberspezifische krankheitsfreie Ein- und 2‑Jahres-Intervall (FFHF) betrug 39% bzw. 32%. Lediglich die Zahl der behandelten Läsionen zeigte sich als prädiktiv für das FFHF. Es starben 16 Patienten, das Ein-und 2‑Jahres-Gesamtüberleben (OS) betrug 64% bzw. 41%. Die Anzahl der behandelten Läsionen und die Child-Pugh-Klasse waren signifikant mit dem OS assoziiert. Schwere akute oder späte Nebenwirkungen (≥Grad 3) traten bei 3% bzw. 8% der Patienten auf. Bei 6 Patienten (17%) wurde eine Lebertransplantation nach SBRT durchgeführt, hiervon zeigten 5 eine komplette pathologische Remission.


Die SBRT (±TACE) bei multipel vorbehandeltem HCC ist effektiv, toxizitätsarm und erzielt eine exzellente Lokalkontrolle. Sie eignet sich als definitive Therapiealternative oder als Überbrückung vor Lebertransplantation. Patienten mit multifokalen Herden zeigten ein signifikant reduziertes Ein- und 2‑Jahres-FFHF und -OS.


Leber Hepatozelluläres Karzinom Körperstereotaktische Bestrahlungstherapie Orthotope Lebertransplantation Multimodale Therapie 


Author Contribution

SG performed data acquisition and participated in patient treatment, statistical analysis, and in drafting the manuscript. CH participated in treatment of the patients and statistical analysis. FW, PP, ED treated the patients and participated in data acquisition. CB revised the manuscript critically. FR participated in data acquisition, statistical analysis, treatment of the patients, drafting the manuscript and critically reviewed the data and the manuscript.

Compliance with ethical guidelines

Conflict of interest

S. Gerum, C. Heinz, C. Belka, F. Walter, P.M. Paprottka, E.N. De Toni, and F. Röder declare that they have no competing interests.

Ethical standards

The study was approved by the Ethics committee of the University of Munich (LMU), reference number 617-16. Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Radiation OncologyUniversity Hospital LMU MunichMunichGermany
  2. 2.Department of Interventional RadiologyUniversity Hospital TU MunichMunichGermany
  3. 3.Department of Internal MedicineUniversity Hospital LMU MunichMunichGermany
  4. 4.CCU Molecular Radiation OncologyGerman Cancer Research CenterHeidelbergGermany
  5. 5.Department of Radiotherapy and Radiation OncologyParacelsus Medical University Salzburg, LandeskrankenhausSalzburgAustria

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