Repeated SBRT for in- and out-of-field recurrences in the liver

  • Eleni GkikaEmail author
  • Iosif Strouthos
  • Simon Kirste
  • Sonja Adebahr
  • Michael Schultheiss
  • Dominik Bettinger
  • Ralph Fritsch
  • Volker Brass
  • Lars Maruschke
  • Hannes Philipp Neeff
  • Sven Arke Lang
  • Ursula Nestle
  • Anca-Ligia Grosu
  • Thomas Baptist Brunner
Original Article



To evaluate the feasibility and toxicity profile of repeated stereotactic body radiotherapy (SBRT) for recurrent primary or secondary liver tumors.


Consecutive patients with primary (hepatocellular carcinoma [HCC] or cholangiocarcinoma [CCC]) or secondary liver cancer (LM), with intrahepatic recurrence or progression after SBRT, underwent re-SBRT in 3 to 12 fractions with a median time of 15 (range 2–66) months between treatments.


In all, 24 patients which were previously treated with SBRT (30 lesions) were retreated with SBRT for “in- and out-of-field” recurrences (2nd SBRT: n = 28, 3rd SBRT: n = 2). The median follow-up after re-irradiation was 14 months. The median prescribed dose for the first SBRT was 46.5 (range 33–66 Gy, EQD210 = 70.5) Gy and 48 (range 27–66 Gy, EQD210 = 71) Gy for the re-SBRT. The median mean liver dose (Dmean, liver) was 6 Gy (range 1–25, EQD22 = 7 Gy) for the first SBRT and 10 Gy (range 1–63 Gy, EQD22 = 9 Gy) for the re-SBRT. Of the 30 re-irradiated lesions 6 were re-irradiated in-field resulting in a median EQD22, maximum of 359 (range 120–500) Gy for both treatments, with an α/β = 2 to account for liver parenchyma. Treatment was well tolerated. Two patients with stent placement before SBRT developed cholangitis 4 and 14 months after re-SBRT. There were no elevations of the serum liver parameters after re-SBRT. One patient developed a grade 3 gastrointestinal bleeding. There was no radiation induced liver disease (RILD) observed.


Repeated liver SBRT is feasible, without excessive liver toxicity, when there is no considerable overlapping with pre-irradiated portions of the stomach or bowel and enough time for the liver to regenerate.


Re-SBRT Hepatocellular carcinoma Cholangiocarcinoma Liver metastases Stereotactic body radiotherapy 



Four-dimensional computed tomography


Barcelona Clinic Liver Cancer


Biological effective doses


Cone beam computed tomography




Eastern Cooperative Oncology Group


Equieffective doses for 2 Gy fractions


Gross tumor volume


Hepatocellular carcinoma


Intensity modulated radiotherapy


Internal target volume


Local control


Organs at risk


Response Evaluation Criteria in Solid Tumors


Radiofrequency ablation


Radiation induced liver disease


Stereotactic body radiotherapy


Simultaneous integrated protection


Selective internal radiation therapy


Standard operating procedures


Transarterial chemoembolization

Wiederholte SBRT bei In- und Out-of-field Rezidiven der Leber



Ziel dieser Analyse war es, die Verträglichkeit und Toxizität wiederholter stereotaktisch fraktionierter Bestrahlung (SBRT) bei primären und sekundären Lebertumoren zu überprüfen.


Patienten mit hepatozellulären Karzinomen (HCC) oder Cholangiokarzinomen (CCC) sowie Patienten mit Lebermetastasen (LM) mit intrahepatischem Progress nach SBRT wurden in 3–12 Fraktionen mittels Re-SBRT behandelt. Das Intervall zwischen der ersten und zweiten SBRT betrug 15 Monate (Spanne 2–66 Monate).


Insgesamt wurden 24 Patienten, die mittels SBRT vorbestrahlt waren (30 Läsionen), bei In- und Out-of field-Rezidiven rebestrahlt (2. SBRT: n = 28; 3. SBRT: n = 2). Das mediane Follow-up nach Re-SBRT betrug 14 Monate. Die mediane verschriebene Dosis am PTV bei der ersten SBRT war 46,5 Gy (Spanne 33–66 Gy; EQD210 = 70,5 Gy) und bei der Re-SBRT 48 Gy (Spanne 27–66 Gy, EQD210 = 71 Gy). Die mediane Dosis im Bereich der Leber (Dmean, „liver“) war 6 Gy (Spanne 1–25 Gy; EQD22 = 7 Gy) bei der ersten SBRT und 10 Gy (Spanne 1–63 Gy; EQD22 = 9 Gy) für die Re-SBRT. Bei den 6 Patienten mit Re-SBRT im Bereich des initialen Planungszielvolumens (PTV, „in-field“) betrug die mediane EQD22, maximum im Bereich der Leber 359 Gy (Spanne 120–500 Gy). Die Therapie wurde gut toleriert. Zwei Patienten mit einem Stent entwickelten 4 und 14 Monate nach Re-SBRT eine Cholangitis. Ein Patient entwickelte eine gastrointestinale Grad-3-Blutung. Es wurde kein Anstieg der Leberenzyme sowie keine radiotherapieassoziierte Lebererkrankung („radiation induced liver disease“, RILD) beobachtet.


Die Re-SBRT im Bereich der Leber ist ohne exzessive Nebenwirkungen möglich, wenn keine signifikante Überlappung mit vorbestrahlten Regionen des Magens und Darms entsteht.


Re-SBRT Hepatozelluläres Karzinom Cholangiokarzinom Lebermetastasen Stereotaktische Strahlentherapie 


Compliance with ethical guidelines

Conflict of interest

E. Gkika, I. Strouthos, S. Kirste, S. Adebahr, M. Schultheiss, D. Bettinger, R. Fritsch, V. Brass, L. Maruschke, H.P. Neeff, S.A. Lang, U. Nestle, A.-L. Grosu and T.B. Brunner declare that they have no competing interests.

Ethical standards

The study was evaluated by the ethics committee of the University Hospital of Freiburg. Consent to publish was obtained. This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

66_2018_1385_MOESM1_ESM.docx (17 kb)
Sup. Table 1 Equieffective doses of 2 Gy (EQD23) to the small bowel and stomach


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Eleni Gkika
    • 1
    • 6
    Email author return OK on get
  • Iosif Strouthos
    • 1
  • Simon Kirste
    • 1
  • Sonja Adebahr
    • 1
  • Michael Schultheiss
    • 2
  • Dominik Bettinger
    • 2
    • 10
  • Ralph Fritsch
    • 3
  • Volker Brass
    • 2
  • Lars Maruschke
    • 4
  • Hannes Philipp Neeff
    • 5
  • Sven Arke Lang
    • 5
  • Ursula Nestle
    • 1
    • 7
    • 8
    • 11
  • Anca-Ligia Grosu
    • 1
    • 7
    • 8
    • 9
  • Thomas Baptist Brunner
    • 1
    • 7
    • 8
    • 9
  1. 1.Departmentof Radiation OncologyUniversity Medical Center FreiburgFreiburg im BreisgauGermany
  2. 2.Department of Gastroenterology, Hepatology, Endocrinology and Infectious DiseasesUniversity Medical Center FreiburgFreiburgGermany
  3. 3.Department of Internal Medicine, Hematology, Oncology and Stem-Cell TransplantationUniversity Medical Center FreiburgFreiburgGermany
  4. 4.Department of RadiologyUniversity Medical Center FreiburgFreiburgGermany
  5. 5.Department of General and Visceral SurgeryUniversity Medical Center FreiburgFreiburgGermany
  6. 6.University Medical Center FreiburgFreiburgGermany
  7. 7.Partner Site FreiburgGerman Cancer Consortium (DKTK)FreiburgGermany
  8. 8.Faculty of MedicineUniversity of FreiburgFreiburgGermany
  9. 9.German cancer Research Center (DKFZ)HeidelbergGermany
  10. 10.Berta-Ottenstein-Programme, Faculty of MedicineUniversity of FreiburgFreiburgGermany
  11. 11.Department of Radiation OncologyKliniken Maria HilfMönchengladbachGermany

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