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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
  • 67 Downloads

Abstract

Purpose

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

Methods

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.

Results

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.

Conclusions

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.

Keywords

Re-SBRT Hepatocellular carcinoma Cholangiocarcinoma Liver metastases Stereotactic body radiotherapy 

Abbreviations

4D CT

Four-dimensional computed tomography

BCLC

Barcelona Clinic Liver Cancer

BED

Biological effective doses

CBCT

Cone beam computed tomography

CTP

Child-Turcotte-Pugh

ECOG

Eastern Cooperative Oncology Group

EQD2

Equieffective doses for 2 Gy fractions

GTV

Gross tumor volume

HCC

Hepatocellular carcinoma

IMRT

Intensity modulated radiotherapy

ITV

Internal target volume

LC

Local control

OARs

Organs at risk

RECIST

Response Evaluation Criteria in Solid Tumors

RFA

Radiofrequency ablation

RILD

Radiation induced liver disease

SBRT

Stereotactic body radiotherapy

SIP

Simultaneous integrated protection

SIRT

Selective internal radiation therapy

SOPs

Standard operating procedures

TACE

Transarterial chemoembolization

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

Zusammenfassung

Zielsetzung

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

Methoden

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).

Ergebnisse

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.

Schlussfolgerung

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

Schlüsselwörter

Re-SBRT Hepatozelluläres Karzinom Cholangiokarzinom Lebermetastasen Stereotaktische Strahlentherapie 

Notes

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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