Advertisement

Strahlentherapie und Onkologie

, Volume 193, Issue 10, pp 823–830 | Cite as

Interobserver variability in target volume delineation of hepatocellular carcinoma

An analysis of the working group “Stereotactic Radiotherapy” of the German Society for Radiation Oncology (DEGRO)
  • E. Gkika
  • S. Tanadini-Lang
  • S. Kirste
  • P. A. Holzner
  • H. P. Neeff
  • H. C. Rischke
  • T. Reese
  • F. Lohaus
  • M. N. Duma
  • K. Dieckmann
  • R. Semrau
  • M. Stockinger
  • D. Imhoff
  • N. Kremers
  • M. F. Häfner
  • N. Andratschke
  • U. Nestle
  • A. L. Grosu
  • M. Guckenberger
  • T. B. Brunner
Original Article

Abstract

Background

Definition of gross tumor volume (GTV) in hepatocellular carcinoma (HCC) requires dedicated imaging in multiple contrast medium phases. The aim of this study was to evaluate the interobserver agreement (IOA) in gross tumor delineation of HCC in a multicenter panel.

Methods

The analysis was performed within the “Stereotactic Radiotherapy” working group of the German Society for Radiation Oncology (DEGRO). The GTVs of three anonymized HCC cases were delineated by 16 physicians from nine centers using multiphasic CT scans. In the first case the tumor was well defined. The second patient had multifocal HCC (one conglomerate and one peripheral tumor) and was previously treated with transarterial chemoembolization (TACE). The peripheral lesion was adjacent to the previous TACE site. The last patient had an extensive HCC with a portal vein thrombosis (PVT) and an inhomogeneous liver parenchyma due to cirrhosis. The IOA was evaluated according to Landis and Koch.

Results

The IOA for the first case was excellent (kappa: 0.85); for the second case moderate (kappa: 0.48) for the peripheral tumor and substantial (kappa: 0.73) for the conglomerate. In the case of the peripheral tumor the inconsistency is most likely explained by the necrotic tumor cavity after TACE caudal to the viable tumor. In the last case the IOA was fair, with a kappa of 0.34, with significant heterogeneity concerning the borders of the tumor and the PVT.

Conclusion

The IOA was very good among the cases were the tumor was well defined. In complex cases, where the tumor did not show the typical characteristics, or in cases with Lipiodol (Guerbet, Paris, France) deposits, IOA agreement was compromised.

Keywords

Stereotactic body radiotherapy Computed tomography Toxicity SBRT GTV delineation GTV definition 

Interobservervariabilität bei der Zielvolumendefinition für hepatozelluläre Karzinome

Eine Analyse der Arbeitsgruppe „Stereotaktische Radiotherapie“ der Deutschen Gesellschaft für Radioonkologie (DEGRO)

Zusammenfassung

Hintergrund

Die Definition des makroskopischen Tumorvolumens (GTV) bei hepatozellulären Karzinomen (HCC) erfordert eine dezidierte Bildgebung in mehreren Kontrastmittelphasen. Ziel dieser Studie war es, die Interobservervariabilität (IOA) bei der Konturierung von HCC-Läsionen durch ein multizentrisches Panel zu evaluieren.

Methoden

Die Analyse wurde von der Arbeitsgruppe Stereotaxie der deutschen Gesellschaft für Radioonkologie (DEGRO) durchgeführt. Die GTVs von 3 anonymisierten HCC-Patienten wurden von 16 Ärzten aus 9 Zentren mit Expertise in der Leberstereotaxie anhand multiphasischer Computertomogramme (CT) beurteilt. Beim ersten Patienten war der Tumor sehr gut abgrenzbar. Der zweite Patient hatte ein multilokuläres HCC (ein Konglomerat und ein peripherer Herd) und war zuvor mittels transarterieller Chemoembolisation (TACE) behandelt worden. Der periphere Herd lag direkt neben der TACE-Stelle. Der dritte Patient hatte einen schwer abzugrenzenden Tumor wegen ausgedehnten Leberinhomogenitäten bei ausgeprägter Leberzirrhose und einer begleitenden Pfortaderthrombose (PVT). Die IOA wurde nach Landis und Koch evaluiert.

Ergebnisse

Die IOA war beim ersten Patienten exzellent (Kappa: 0,85); im zweiten Fall moderat (Kappa: 0,48) für den peripheren Herd und substanziell (Kappa 0,73) für das Konglomerat. Beim peripheren Herd ist diese Inkonsistenz durch TACE kaudal des Tumors entstanden. Beim dritten Patienten war die IOA mit einem Kappa-Wert von 0,34 ausreichend aufgrund signifikanter Heterogenität hinsichtlich der genauen Tumorabgrenzung und dem PVT.

Diskussion

Die IOA war bei den gut abgrenzbaren Tumoren sehr gut. In komplexeren Fällen mit Perfussionsinhomogenitäten oder Lipiodolanreicherung durch Vortherapien war die IOA beeinträchtigt.

Schlüsselwörter

Stereotaktische Strahlentherapie Computertomographie Toxizität SBRT Zielvolumen Definition 

Notes

Acknowledgements

The authors would like to thank G. Rückers for the statistical consulting.

Conflict of interest

E. Gkika, S. Tanadini-Lang, S. Kirste, P.A. Holzner, H.P. Neeff, H.C. Rischke, T. Reese, F. Lohaus, M.N. Duma, K. Dieckmann, R. Semrau, M. Stockinger, D. Imhoff, N. Kremers, M.F. Häfner, N. Andratschke, U. Nestle, A.L. Grosu, M. Guckenberger, and T.B. Brunner declare that they have no competing interests.

Supplementary material

66_2017_1177_MOESM1_ESM.docx (14 kb)
Supplementary Table 1 Fractionation variations

References

  1. 1.
    Bruix J, Gores GJ, Mazzaferro V (2014) Hepatocellular carcinoma: clinical frontiers and perspectives. Gut 63(5):844–855. doi: 10.1136/gutjnl-2013-306627 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Bujold A, Massey CA, Kim JJ, Brierley J, Cho C, Wong RK, Dinniwell RE, Kassam Z, Ringash J, Cummings B, Sykes J, Sherman M, Knox JJ, Dawson LA (2013) Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma. J Clin Oncol 31(13):1631–1639. doi: 10.1200/JCO.2012.44.1659 CrossRefPubMedGoogle Scholar
  3. 3.
    Sterzing F, Brunner TB, Ernst I, Baus WW, Greve B, Herfarth K, Guckenberger M (2014) Stereotactic body radiotherapy for liver tumors: principles and practical guidelines of the DEGRO Working Group on Stereotactic Radiotherapy. Strahlenther Onkol 190(10):872–881. doi: 10.1007/s00066-014-0714-1 CrossRefPubMedGoogle Scholar
  4. 4.
    Verslype C, Rosmorduc O, Rougier P, Group EGW (2012) Hepatocellular carcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 23(Suppl 7):vii41–48. doi: 10.1093/annonc/mds225 CrossRefPubMedGoogle Scholar
  5. 5.
    Landis JR, Koch GG (1977) The measurement of observer agreement for categorical data. Biometrics 33(1):159–174. doi: 10.2307/2529310 CrossRefPubMedGoogle Scholar
  6. 6.
    Zijdenbos APDB, Margolin RA, Palmer AC (1994) Morphometric analysis of white matter lesions in MR images: method and validation. IEEE Trans Med Imaging 13(4):716–724CrossRefPubMedGoogle Scholar
  7. 7.
    Kelemen ASG, Gerig G (1999) Elastic model-based segmentation of 3‑D neuroradiological data sets. IEEE Trans Med Imaging 18(10):828–839CrossRefPubMedGoogle Scholar
  8. 8.
    Beddar AS, Briere TM, Balter P, Pan T, Tolani N, Ng C, Szklaruk J, Krishnan S (2008) 4D-CT imaging with synchronized intravenous contrast injection to improve delineation of liver tumors for treatment planning. Radiother Oncol 87(3):445–448. doi: 10.1016/j.radonc.2007.12.009 CrossRefPubMedGoogle Scholar
  9. 9.
    Hong TS, Bosch WR, Krishnan S, Kim TK, Mamon HJ, Shyn P, Ben-Josef E, Seong J, Haddock MG, Cheng JC, Feng MU, Stephans KL, Roberge D, Crane C, Dawson LA (2014) Interobserver Variability in Target Definition for Hepatocellular Carcinoma With and Without Portal Vein Thrombus: Radiation Therapy Oncology Group Consensus Guidelines. Int J Radiat Oncol Biol Phys 89(4):804–813. doi: 10.1016/j.ijrobp.2014.03.041 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Kim YS, Kim JW, Yoon WS, Kang MK, Lee IJ, Kim TH, Kim JH, Lee HS, Park HC, Jang HS, Kay CS, Yoon SM, Kim MS, Seong J (2016) Interobserver variability in gross tumor volume delineation for hepatocellular carcinoma: Results of Korean Radiation Oncology Group 1207 study. Strahlenther Onkol 192(10):714–721. doi: 10.1007/s00066-016-1028-2 CrossRefPubMedGoogle Scholar
  11. 11.
    Kanematsu M, Semelka RC, Leonardou P, Mastropasqua M, Lee JK (2003) Hepatocellular carcinoma of diffuse type: MR imaging findings and clinical manifestations. J Magn Reson Imaging 18(2):189–195. doi: 10.1002/jmri.10336 CrossRefPubMedGoogle Scholar
  12. 12.
    Baron RL, Brancatelli G (2004) Computed tomographic imaging of hepatocellular carcinoma. Gastroenterology 127(5):133–S143. doi: 10.1053/j.gastro.2004.09.027 CrossRefGoogle Scholar
  13. 13.
    European Association for the Study of the Liver, European Organisation for Research and Treatment of Cancer (2012) EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 56(4):908–943. doi: 10.1016/j.jhep.2011.12.001 CrossRefGoogle Scholar
  14. 14.
    Tsurusaki M, Sofue K, Isoda H, Okada M, Kitajima K, Murakami T (2016) Comparison of gadoxetic acid-enhanced magnetic resonance imaging and contrast-enhanced computed tomography with histopathological examinations for the identification of hepatocellular carcinoma: a multicenter phase III study. J Gastroenterol 51(1):71–79. doi: 10.1007/s00535-015-1097-5 CrossRefPubMedGoogle Scholar
  15. 15.
    Chou R, Cuevas C, Fu R, Devine B, Wasson N, Ginsburg A, Zakher B, Pappas M, Graham E, Sullivan SD (2015) Imaging techniques for the diagnosis of Hepatocellular carcinoma: a systematic review and meta-analysis. Ann Intern Med 162(10):697–711. doi: 10.7326/M14-2509 CrossRefPubMedGoogle Scholar
  16. 16.
    Lee YJ, Lee JM, Lee JS, Lee HY, Park BH, Kim YH, Han JK, Choi BI (2015) Hepatocellular carcinoma: diagnostic performance of multidetector CT and MR imaging – a systematic review and meta-analysis. Radiology 275(1):97–109. doi: 10.1148/radiol.14140690 CrossRefPubMedGoogle Scholar
  17. 17.
    Heimbach J, Kulik LM, Finn R, Sirlin CB, Abecassis M, Roberts LR, Zhu A, Murad MH, Marrero J (2017) Aasld guidelines for the treatment of hepatocellular carcinoma. Hepatology. doi: 10.1002/hep.29086 Google Scholar
  18. 18.
    Nestle U, Rischke HC, Eschmann SM, Holl G, Tosch M, Miederer M, Plotkin M, Essler M, Puskas C, Schimek-Jasch T, Duncker-Rohr V, Ruhl F, Leifert A, Mix M, Grosu AL, Konig J, Vach W (2015) Improved inter-observer agreement of an expert review panel in an oncology treatment trial – Insights from a structured interventional process. Eur J Cancer 51(17):2525–2533. doi: 10.1016/j.ejca.2015.07.036 CrossRefPubMedGoogle Scholar
  19. 19.
    Schimek-Jasch T, Troost EG, Rucker G, Prokic V, Avlar M, Duncker-Rohr V, Mix M, Doll C, Grosu AL, Nestle U (2015) A teaching intervention in a contouring dummy run improved target volume delineation in locally advanced non-small cell lung cancer: Reducing the interobserver variability in multicentre clinical studies. Strahlenther Onkol 191(6):525–533. doi: 10.1007/s00066-015-0812-8 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Deutschland 2017

Authors and Affiliations

  • E. Gkika
    • 1
  • S. Tanadini-Lang
    • 2
  • S. Kirste
    • 1
  • P. A. Holzner
    • 3
  • H. P. Neeff
    • 3
  • H. C. Rischke
    • 1
    • 4
  • T. Reese
    • 5
  • F. Lohaus
    • 6
    • 14
    • 15
    • 16
    • 21
  • M. N. Duma
    • 7
    • 19
  • K. Dieckmann
    • 8
  • R. Semrau
    • 9
  • M. Stockinger
    • 10
  • D. Imhoff
    • 11
    • 20
  • N. Kremers
    • 12
  • M. F. Häfner
    • 13
  • N. Andratschke
    • 2
  • U. Nestle
    • 1
    • 17
    • 18
    • 22
  • A. L. Grosu
    • 1
    • 17
    • 18
    • 22
  • M. Guckenberger
    • 2
  • T. B. Brunner
    • 1
    • 17
    • 18
    • 22
  1. 1.Department of Radiation OncologyMedical Center – University of FreiburgFreiburg im BreisgauGermany
  2. 2.Department of Radiation OncologyUniversity Hospital ZürichZurichSwitzerland
  3. 3.Department of Visceral SurgeryMedical Center – University of FreiburgFreiburgGermany
  4. 4.Department of Nuclear MedicineMedical Center – University of FreiburgFreiburgGermany
  5. 5.Department of Radiation OncologyUniversity Hospital Halle-WittenbergHalle-WittenbergGermany
  6. 6.Department of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav CarusTechnische Universität DresdenDresdenGermany
  7. 7.Institute of Innovative Radiotherapy, Department of Radiation SciencesHelmholtz Zentrum MunichMunichGermany
  8. 8.Department of Radiation Oncology, General Hospital ViennaMedical University ViennaViennaAustria
  9. 9.Department of Radiation OncologyUniversity Hospital of CologneCologneGermany
  10. 10.Department of Radiation OncologyUniversity Hospital MainzMainzGermany
  11. 11.Department of Radiation OncologyUniversity Hospital FrankfurtFrankfurtGermany
  12. 12.Department of RadiologyMedical Center – University of FreiburgFreiburgGermany
  13. 13.Department of Radiation OncologyUniversity Hospital HeidelbergHeidelbergGermany
  14. 14.German Cancer Research Center (DKFZ)HeidelbergGermany
  15. 15.OncoRay – National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav CarusTechnische Universität DresdenDresdenGermany
  16. 16.National Center for Tumor Diseases (NCT)DresdenGermany
  17. 17.Faculty of MedicineUniversity of FreiburgFreiburgGermany
  18. 18.partner site FreiburgGerman Cancer Consortium (DKTK)FreiburgGermany
  19. 19.Department of Radiation Oncology, Klinikum Rechts der IsarTU MunichMunichGermany
  20. 20.Saphir Radiosurgery CenterFrankfurtGermany
  21. 21.German Cancer Consortium (DKTK) partner site DresdenDresdenGermany
  22. 22.German cancer Research Center (DKFZ)HeidelbergGermany

Personalised recommendations