Download PDF
Z Gastroenterol 2020; 58(01): 39-47
DOI: 10.1055/a-1072-6683
Originalarbeit
© Georg Thieme Verlag KG Stuttgart · New York

Monozentrische Erfahrungen mit stereotaktischer Bestrahlung (SBRT) beim fortgeschrittenen hepatozellulären Karzinom im Stadium BCLC-C

Monocentric experiences of stereotactic body radiation therapy (SBRT) for advanced hepatocellular carcinomas (BCLC-C)
Carolin Czauderna
1   I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz, Mainz, Deutschland
,
Marcus Stockinger
2   Klinik und Poliklinik für Radioonkologie und Strahlentherapie, Universitätsmedizin Mainz, Mainz, Deutschland
,
Anne Ebersberger
2   Klinik und Poliklinik für Radioonkologie und Strahlentherapie, Universitätsmedizin Mainz, Mainz, Deutschland
,
Heinz Schmidberger
2   Klinik und Poliklinik für Radioonkologie und Strahlentherapie, Universitätsmedizin Mainz, Mainz, Deutschland
,
Lukas Müller
3   Klinik und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsmedizin Mainz, Mainz, Deutschland
,
Roman Kloeckner
3   Klinik und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsmedizin Mainz, Mainz, Deutschland
,
Christoph Düber
3   Klinik und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsmedizin Mainz, Mainz, Deutschland
,
Arndt Weinmann
1   I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz, Mainz, Deutschland
,
Peter R. Galle
1   I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz, Mainz, Deutschland
,
Jens U. Marquardt
1   I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz, Mainz, Deutschland
4   Medizinische Klinik I, Universitätsklinikum Schleswig-Holstein – Campus Lübeck, Lübeck, Deutschland
› Author Affiliations
Further Information

Publication History

22 August 2019

29 November 2019

Publication Date:
13 January 2020 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Hepatozelluläre Karzinome (HCC) sind durch eine schlechte Prognose und limitierte Behandlungsoptionen in fortgeschrittenen Stadien gekennzeichnet. Die Behandlung erfordert daher interdisziplinäre Diskussion und multimodale Therapiekonzepte. Neben etablierten lokoregionalen sowie systemischen Therapieansätzen gewinnt die stereotaktische Bestrahlung (SBRT, stereotactic body radiation therapy) zunehmend an Bedeutung. Ergebnisse früher klinischer Studien weisen auf hohe lokale Kontrollraten bei einem akzeptablen Toxizitätsprofil hin. In der vorliegenden Arbeit beschreiben wir die monozentrischen Erfahrungen zur SBRT bei fortgeschrittener HCC-Erkrankung (BCLC-C) in einem universitären Tumorzentrum.

Insgesamt zehn Patienten mit insgesamt 16 SBRT Behandlungen wurden in die Fallsammlung aufgenommen und retrospektiv ausgewertet. Alle Patienten wiesen ein fortgeschrittenes Stadium mit vaskulärer Invasion und/oder Metastasen unter erhaltener Leberfunktion auf. Zwei Patienten wurden ausschließlich mittels SBRT, zwei nach TACE und sechs Patienten zusätzlich mit einer Systemtherapie behandelt. Bestrahlt wurden in den meisten Fällen intrahepatische Herde (n = 7), darüber hinaus Tumorthrombosen und Lymphknoten- sowie Knochenmetastasen. Bestrahlt wurde in einer, drei und fünf Fraktionen zu Gesamtdosen von durchschnittlich 38 Gy. Wir beobachteten ein gutes Ansprechen der bestrahlten Läsionen (73 % nach drei Monaten; 66 % nach sechs Monaten) bei insgesamt guter Verträglichkeit der SBRT. Auch in der Kombination mit lokoregionalen Verfahren bzw. Systemtherapien kam es zu keinen schwerwiegenden Komplikationen.

Zusammenfassend stützen unsere Erfahrungen die Ergebnisse der frühen klinischen Studien und deuten auf eine sichere Anwendung der SBRT mit einer guten lokalen Kontrolle auch bei fortgeschrittener HCC-Erkrankung mit erhaltener Leberfunktion hin.

Abstract

Hepatocellular carcinomas (HCCs) are highly malignant primary liver cancers with poor prognosis and limited treatment options in advanced stages of disease. Treatment of HCC requires interdisciplinary discussion and multimodal therapy approaches. Beside established loco-regional and systemic therapies, stereotactic body radiation therapy (SBRT) gained increasing importance over recent years. First results of early clinical studies indicate high rates of local control with a good safety profile. In the present work, we evaluated our single center experiences with SBRT in patients with advanced HCCs.

Ten patients with 16 SBRTs were included and retrospectively analyzed in this case collection. All patients presented in advanced tumor stages with vascular invasion and/or metastases, but preserved liver function. Two patients were treated only with SBRT, two after TACE and six patients received SBRT in addition to systemic therapy. In most of the cases SBRT were applied to intrahepatic lesions. Large tumor thromboses, lymph nodes as well as bone metastases were irradiated in one, three and five fractions with a median overall dose of 38 Gy. We observed a good local tumor control with a good safety profile in all cases. No severe complications occurred in combination to sequential as well as additive approach to loco-regional or systemic treatments.

In conclusion, our experiences confirm results of early clinical studies indicating safe use and good local control rates also in advanced stages of HCC with preserved liver function.

Schlüsselwörter

Leberzirrhose - hepatozelluläres Karzinom - stereotaktische Bestrahlung - RILD

Key words

liver cirrhosis - hepatocellular carcinoma - stereotactic body radiation therapy - RILD
 

  • References

  • 1 El-Serag HB. Hepatocellular carcinoma. N Engl J Med 2011; 365: 1118-1127
    CrossrefPubMedGoogle Scholar
  • 2 Bray F. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68: 394-424
    PubMedGoogle Scholar
  • 3 Liu Z. et al. The trends in incidence of primary liver cancer caused by specific etiologies: Results from the Global Burden of Disease Study 2016 and implications for liver cancer prevention. J Hepatol 2019; 70: 674-683
    CrossrefPubMedGoogle Scholar
  • 4 Njei B, Ditah I, Lim JK. Emerging trends in hepatocellular carcinoma incidence and mortality. Hepatology 2015; 61: 191-199
    CrossrefPubMedGoogle Scholar
  • 5 Czauderna C. et al. Hepatocellular carcinoma. Internist (Berl) 2017; 58: 469-479
    CrossrefPubMedGoogle Scholar
  • 6 Younossi ZM. et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016; 64: 73-84
    CrossrefPubMedGoogle Scholar
  • 7 Fujiwara N. et al. Risk factors and prevention of hepatocellular carcinoma in the era of precision medicine. J Hepatol 2018; 68: 526-549
    CrossrefPubMedGoogle Scholar
  • 8 Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 1999; 19: 329-338
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 European Association for the Study of the Liver. Electronic address, e.e.e. and L. European Association for the Study of the, EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2018; 69: 182-236
    CrossrefPubMedGoogle Scholar
  • 10 Heimbach JK. et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2018; 67: 358-380
    CrossrefPubMedGoogle Scholar
  • 11 Mazzaferro V. et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996; 334: 693-699
    CrossrefPubMedGoogle Scholar
  • 12 Cheng AL. et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 2009; 10: 25-34
    CrossrefPubMedGoogle Scholar
  • 13 Bruix J. et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017; 389: 56-66
    CrossrefPubMedGoogle Scholar
  • 14 Kudo M. et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet 2018; 391: 1163-1173
    CrossrefPubMedGoogle Scholar
  • 15 Abou-Alfa GK. et al. Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma. N Engl J Med 2018; 379: 54-63
    CrossrefPubMedGoogle Scholar
  • 16 Zhu AX. et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased alpha-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2019; 20: 282-296
    CrossrefPubMedGoogle Scholar
  • 17 Soni PD, Palta M. Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: Current State and Future Opportunities. Dig Dis Sci 2019; 64: 1008-1015
    CrossrefPubMedGoogle Scholar
  • 18 Rim, C.H., H.J. Kim, and J. Seong. Clinical feasibility and efficacy of stereotactic body radiotherapy for hepatocellular carcinoma: A systematic review and meta-analysis of observational studies. Radiother Oncol 2019; 131: 135-144
    CrossrefPubMedGoogle Scholar
  • 19 Berman AT. et al. Empiric Radiotherapy for Lung Cancer Collaborative Group multi-institutional evidence-based guidelines for the use of empiric stereotactic body radiation therapy for non-small cell lung cancer without pathologic confirmation. Transl Lung Cancer Res 2019; 8: 5-14
    PubMedGoogle Scholar
  • 20 Blakaj A. et al. Review and current state of radiation therapy for locally advanced pancreatic adenocarcinoma. J Gastrointest Oncol 2018; 9: 1027-1036
    CrossrefPubMedGoogle Scholar
  • 21 Beckta JM, Nosrati JD, Yu JB. Moderate hypofractionation and stereotactic body radiation therapy in the treatment of prostate cancer. Urol Oncol 2019; 37: 619-627
    CrossrefPubMedGoogle Scholar
  • 22 Palma DA. et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial. Lancet 2019; 393: 2051-2058
    CrossrefPubMedGoogle Scholar
  • 23 Sapisochin G. et al. Stereotactic body radiotherapy vs. TACE or RFA as a bridge to transplant in patients with hepatocellular carcinoma. An intention-to-treat analysis. J Hepatol 2017; 67: 92-99
    CrossrefPubMedGoogle Scholar
  • 24 Hara K. et al. Radiotherapy for Hepatocellular Carcinoma Results in Comparable Survival to Radiofrequency Ablation: A Propensity Score Analysis. Hepatology 2019; 69: 2533-2545
    CrossrefPubMedGoogle Scholar
  • 25 Yoon SM. et al. Efficacy and Safety of Transarterial Chemoembolization Plus External Beam Radiotherapy vs Sorafenib in Hepatocellular Carcinoma With Macroscopic Vascular Invasion: A Randomized Clinical Trial. JAMA Oncol 2018; 4: 661-669
    CrossrefPubMedGoogle Scholar
  • 26 Shui Y. et al. Stereotactic body radiotherapy based treatment for hepatocellular carcinoma with extensive portal vein tumor thrombosis. Radiat Oncol 2018; 13: 188
    CrossrefPubMedGoogle Scholar
  • 27 Gerum S. et al. Stereotactic body radiation therapy (SBRT) in patients with hepatocellular carcinoma and oligometastatic liver disease. Radiat Oncol 2018; 13: 100
    CrossrefPubMedGoogle Scholar
  • 28 Zhong NB, Lv GM, Chen ZH. Stereotactic body radiotherapy combined with transarterial chemoembolization for huge (>/=10 cm) hepatocellular carcinomas: A clinical study. Mol Clin Oncol 2014; 2: 839-844
    CrossrefPubMedGoogle Scholar
  • 29 Bujold A. et al. Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma. J Clin Oncol 2013; 31: 1631-1639
    CrossrefPubMedGoogle Scholar
  • 30 Brade AM. et al. Phase 1 Trial of Sorafenib and Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma. Int J Radiat Oncol Biol Phys 2016; 94: 580-587
    CrossrefPubMedGoogle Scholar
  • 31 Takeda A. et al. Phase 2 study of stereotactic body radiotherapy and optional transarterial chemoembolization for solitary hepatocellular carcinoma not amenable to resection and radiofrequency ablation. Cancer 2016; 122: 2041-2049
    CrossrefPubMedGoogle Scholar
  • 32 Bruix J, Sherman M. American Association for the Study of Liver. Management of hepatocellular carcinoma: an update. Hepatology 2011; 53: 1020-1022
    CrossrefPubMedGoogle Scholar
  • 33 Weinmann A. et al. Trends in epidemiology, treatment, and survival of hepatocellular carcinoma patients between 1998 and 2009: an analysis of 1066 cases of a German HCC Registry. J Clin Gastroenterol 2014; 48: 279-289
    CrossrefPubMedGoogle Scholar
  • 34 Munoz-Schuffenegger P, Ng S, Dawson LA. Radiation-Induced Liver Toxicity. Semin Radiat Oncol 2017; 27: 350-357
    CrossrefPubMedGoogle Scholar
  • 35 Wong TC. et al. Better survival after stereotactic body radiation therapy following transarterial chemoembolization in nonresectable hepatocellular carcinoma: A propensity score matched analysis. Surg Oncol 2019; 28: 228-235
    CrossrefPubMedGoogle Scholar
  • 36 Bettinger D. et al. Stereotactic Body Radiation Therapy as an Alternative Treatment for Patients with Hepatocellular Carcinoma Compared to Sorafenib: A Propensity Score Analysis. Liver Cancer 2019; 8: 281-294 . doi: 10.1159/000490260
    CrossrefPubMedGoogle Scholar
  • 37 Twyman-Saint VC. et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature 2015; 520: 373-377
    PubMedGoogle Scholar
  • 38 Formenti SC, Demaria S. Combining radiotherapy and cancer immunotherapy: a paradigm shift. J Natl Cancer Inst 2013; 105: 256-265
    CrossrefPubMedGoogle Scholar
  • 39 Dreher C. et al. Metabolic liver function after stereotactic body radiation therapy for hepatocellular carcinoma. Acta Oncol 2016; 55: 886-891
    CrossrefPubMedGoogle Scholar
  • 40 Jung J. et al. Radiation-induced liver disease after stereotactic body radiotherapy for small hepatocellular carcinoma: clinical and dose-volumetric parameters. Radiat Oncol 2013; 8: 249
    CrossrefPubMedGoogle Scholar
  • 41 Lasley FD. et al. Treatment variables related to liver toxicity in patients with hepatocellular carcinoma, Child-Pugh class A and B enrolled in a phase 1–2 trial of stereotactic body radiation therapy. Pract Radiat Oncol 2015; 5: e443-e449
    CrossrefPubMedGoogle Scholar