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

Stereotaktische Bestrahlungstherapie bei Patienten mit hepatozellulärem Karzinom im Rahmen multimodaler Behandlung

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Abstract

Purpose

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

Methods

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).

Results

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.

Conclusion

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.

Zusammenfassung

Ziel

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

Methoden

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).

Ergebnisse

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.

Schlussfolgerung

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.

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Abbreviations

4D-CT:

four-dimensional computed tomography

AFP:

alpha-fetoprotein

BCLC:

Barcelona Clinical Liver Cancer

BED:

biologically effective dose

CBCT:

cone beam computed tomography

ccm:

cubic centimeters

CP class:

Child–Pugh class

CT:

computed tomography

CTCAE:

Common Toxicity Criteria for Adverse Events

FFHF:

freedom from hepatic failure

GTV:

gross tumor volume

HCC:

hepatocellular carcinoma

IF:

in-field

IMRT:

intensity-modulated radiation therapy

ITV:

internal target volume

KPS:

Karnofsky performance score

LC:

local control

LR:

local recurrence

MRI:

magnetic resonance imaging

OLT:

orthotopic liver transplantation

OS:

overall survival

pCR:

pathologic complete response

PFS:

progression-free survival

pPR:

pathologic partial response

PTV:

planning target volume

RFA:

radiofrequency ablation

RILD:

radiation-induced liver disease

SBRT:

stereotactic body radiation therapy

SIRT:

selective internal radiotherapy

TACE:

transarterial chemoembolization

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Author information

Authors and Affiliations

  1. Department of Radiation Oncology, University Hospital LMU Munich, Marchioninistr. 15, 81377, Munich, Germany

    Sabine Gerum, Christian Heinz, Claus Belka, Franziska Walter & Falk Roeder

  2. Department of Interventional Radiology, University Hospital TU Munich, Ismaninger Str. 22, 81675, Munich, Germany

    Philipp Marius Paprottka

  3. Department of Internal Medicine, University Hospital LMU Munich, Marchioninistr. 15, 81377, Munich, Germany

    Enrico N De Toni

  4. CCU Molecular Radiation Oncology, German Cancer Research Center, Heidelberg, Germany

    Falk Roeder

  5. Department of Radiotherapy and Radiation Oncology, Paracelsus Medical University Salzburg, Landeskrankenhaus, Müllner Hauptstraße 48, 5022, Salzburg, Austria

    Sabine Gerum & Falk Roeder

Authors
  1. Sabine Gerum
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  2. Christian Heinz
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  3. Claus Belka
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  4. Franziska Walter
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  5. Philipp Marius Paprottka
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  6. Enrico N De Toni
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  7. Falk Roeder
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Contributions

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.

Corresponding author

Correspondence to Falk Roeder.

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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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Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Gerum, S., Heinz, C., Belka, C. et al. Stereotactic body radiotherapy in patients with hepatocellular carcinoma in a multimodal treatment setting. Strahlenther Onkol 196, 334–348 (2020). https://doi.org/10.1007/s00066-019-01540-8

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  • DOI: https://doi.org/10.1007/s00066-019-01540-8

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