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Strahlentherapie und Onkologie

, Volume 194, Issue 2, pp 156–163 | Cite as

Radiation-induced liver injury mimicking liver metastases on FDG-PET-CT after chemoradiotherapy for esophageal cancer

A retrospective study and literature review
  • Francine E. M. Voncken
  • Berthe M. P. Aleman
  • Jolanda M. van Dieren
  • Cecile Grootscholten
  • Ferry Lalezari
  • Johanna W. van Sandick
  • Jeffrey D. Steinberg
  • Erik Vegt
Original Article

Abstract

Background

For esophageal cancer patients treated with neoadjuvant chemoradiotherapy (nCRT), restaging using F‑18-fluorodeoxyglucose (FDG) positron emission tomography computed tomography (PET-CT) following nCRT can detect interval metastases, including liver metastases, in almost 10% of patients. However, in clinical practice, focal FDG liver uptake, unrelated to liver metastases, is observed after chemoradiotherapy. This radiation-induced liver injury (RILI) can potentially lead to overstaging.

Methods

A systematic search for potential cases of RILI after (chemo)radiotherapy for esophageal cancer was performed in the electronic reports from all PET-CT scans made between 2006 and 2015 in our hospital. Additional data about potential cases were obtained from the electronic medical records. A literature review of RILI was also performed.

Results

Of 205 patients undergoing nCRT, 6 cases with localized increased FDG uptake in the caudate or left liver lobe following nCRT for esophageal cancer were identified. None of these patients had signs of liver metastases with additional imaging, during surgery, on biopsy, or during follow-up (range 11–46 months). At our institute, the incidence of RILI after neoadjuvant chemoradiotherapy for esophageal cancer was 3%. In the literature, RILI is described in about 8% of patients at the time of restaging. FDG-avid lesions occur in the high radiation dose area, usually corresponding to the caudate or left liver lobe.

Conclusions

FDG accumulation in the caudate or left liver lobe after CRT in the area that received a high radiation dose may be caused by metastases or RILI. Awareness of the pitfall of high FDG uptake in RILI is crucial to avoid misinterpretation and overstaging.

Keywords

Fluorodeoxyglucose f18 Positron emission tomography-computed tomography Esophageal neoplasms Radiation effects and adverse reactions False positive reactions 

Strahlungsinduzierte Leberschäden ähneln Lebermetastasen im FDG-PET-CT nach Radiochemotherapie beim Ösophaguskarzinom

Eine retrospektive Studie und Literatursuche

Zusammenfassung

Hintergrund

Nach neoadjuvanter Radiochemotherapie (nCRT) findet man bei ungefähr 10 % der Patienten mit Ösophaguskarzinom beim Restaging in der F‑18-Fluorodeoxyglukose-Positronenemissionscomputertomographie (FDG-PET-CT) Intervallmetastasen, einschließlich Lebermetastasen. In der klinischen Praxis wird aber nach CRT ebenfalls eine fokale FDG-Aufnahme in der Leber beobachtet, die nicht durch Lebermetastasen erklärt werden kann. Dieser strahlungsinduzierte Leberschaden (RILI) kann ein „Overstaging“ verursachen.

Methoden

In unserer Klinik wurde in den elektronischen Aufzeichnungen aus allen PET-CT-Scans zwischen 2006 und 2015 systematisch nach möglichen Patienten mit RILI nach nCRT beim Ösophaguskarzinom gesucht. Zusätzliche Daten über potenzielle Fälle wurden aus den elektronischen Patientenakten entnommen. Zudem wurde eine Literatursuche zu RILI durchgeführt.

Ergebnisse

Insgesamt wurden 205 Patienten mit nCRT behandelt, von denen 6 Patienten mit lokal erhöhter FDG-Aufnahme im Lobus caudatus oder linken Lebersegment nach nCRT aufgrund eines Ösophaguskarzinoms identifiziert wurden. Keiner dieser Patienten hatte Anzeichen von Lebermetastasen bei zusätzlicher Bildgebung, während der Operation, bei Biopsie oder während des Follow-up (Spanne 11–46 Monate). In unserem Institut betrug die Inzidenz von RILI nach nCRT beim Ösophaguskarzinom 3 %. In der Literatur wird ein RILI bei circa 8 % der Patienten während dem Restaging beschrieben. FDG-avide Läsionen treten besonders im hohen Strahlendosisbereich auf, und dann in der Regel im Lobus caudatus oder linken Lebersegment.

Schlussfolgerung

FDG-Akkumulationen im Lobus caudatus oder linken Lebersegment nach CRT im hohen Strahlendosisbereich können sowohl durch Metastasen als auch durch einen RILI verursacht werden. Differenzialdiagnostisch ist ein RILI mit zu erwägen, um Fehlinterpretationen und ein Overstaging zu vermeiden.

Schlüsselwörter

F-18-Fluorodeoxyglukose Positronenemissionstomographie mit Computertomographie Ösophagusneoplasien Strahlungsinduzierte Nebenwirkungen Falsch-positive Reaktionen 

Notes

Acknowledgements

The authors would like to thank Matthias Karger for his help on the German translation of the abstract.

Conflict of interest

F.E.M. Voncken, B.M.P. Aleman, J.M. van Dieren, C. Grootscholten, F. Lalezari, J.W. van Sandick, J.D. Steinberg and E. Vegt declare that they have no competing interests.

References

  1. 1.
    Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, Forman D, Bray F (2013) Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 49(6):1374–1403.  https://doi.org/10.1016/j.ejca.2012.12.027 CrossRefPubMedGoogle Scholar
  2. 2.
    Heeren PA, Jager PL, Bongaerts F, van Dullemen H, Sluiter W, Plukker JT (2004) Detection of distant metastases in esophageal cancer with (18)F-FDG PET. J Nucl Med 45(6):980–987PubMedGoogle Scholar
  3. 3.
    Bruzzi JF, Munden RF, Truong MT, Marom EM, Sabloff BS, Gladish GW, Iyer RB, Pan TS, Macapinlac HA, Erasmus JJ (2007) PET/CT of esophageal cancer: its role in clinical management. Radiographics 27(6):1635–1652.  https://doi.org/10.1148/rg.276065742 CrossRefPubMedGoogle Scholar
  4. 4.
    Shapiro J, van Lanschot JJ, Hulshof MC, van Hagen P, van Berge Henegouwen MI, Wijnhoven BP, van Laarhoven HW, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, Ten KFJ, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Bilgen EJ, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, Steyerberg EW, van der Gaast A, group Cs (2015) Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol 16(9):1090–1098.  https://doi.org/10.1016/S1470-2045(15)00040-6 CrossRefPubMedGoogle Scholar
  5. 5.
    Sjoquist KM, Burmeister BH, Smithers BM, Zalcberg JR, Simes RJ, Barbour A, Gebski V, Australasian Gastro-Intestinal Trials G (2011) Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol 12(7):681–692.  https://doi.org/10.1016/S1470-2045(11)70142-5 CrossRefPubMedGoogle Scholar
  6. 6.
    Stiekema J, Vermeulen D, Vegt E, Voncken FE, Aleman BM, Sanders J, Boot H, van Sandick JW (2014) Detecting interval metastases and response assessment using 18F-FDG PET/CT after neoadjuvant chemoradiotherapy for esophageal cancer. Clin Nucl Med 39(10):862–867.  https://doi.org/10.1097/RLU.0000000000000517 CrossRefPubMedGoogle Scholar
  7. 7.
    Nijkamp J, Rossi M, Lebesque J, Belderbos J, van den Heuvel M, Kwint M, Uyterlinde W, Vogel W, Sonke JJ (2013) Relating acute esophagitis to radiotherapy dose using FDG-PET in concurrent chemo-radiotherapy for locally advanced non-small cell lung cancer. Radiother Oncol 106(1):118–123.  https://doi.org/10.1016/j.radonc.2012.09.024 CrossRefPubMedGoogle Scholar
  8. 8.
    Ulaner GA, Lyall A (2013) Identifying and distinguishing treatment effects and complications from malignancy at FDG PET/CT. Radiographics 33(6):1817–1834.  https://doi.org/10.1148/rg.336125105 CrossRefPubMedGoogle Scholar
  9. 9.
    Yamasaki SA, Marn CS, Francis IR, Robertson JM, Lawrence TS (1995) High-dose localized radiation therapy for treatment of hepatic malignant tumors: CT findings and their relation to radiation hepatitis. AJR Am J Roentgenol 165(1):79–84.  https://doi.org/10.2214/ajr.165.1.7785638 CrossRefPubMedGoogle Scholar
  10. 10.
    Edge SB, Compton CC (2010) The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 17(6):1471–1474.  https://doi.org/10.1245/s10434-010-0985-4 CrossRefPubMedGoogle Scholar
  11. 11.
    Grant MJ, Didier RA, Stevens JS, Beyder DD, Hunter JG, Thomas CR, Coakley FV (2014) Radiation-induced liver disease as a mimic of liver metastases at serial PET/CT during neoadjuvant chemoradiation of distal esophageal cancer. Abdom Imaging 39(5):963–968.  https://doi.org/10.1007/s00261-014-0125-x CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Iyer RB, Balachandran A, Bruzzi JF, Johnson V, Macapinlac HA, Munden RF (2007) PET/CT and hepatic radiation injury in esophageal cancer patients. Cancer Imaging 7:189–194.  https://doi.org/10.1102/1470-7330.2007.0027 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Pan CC, Kavanagh BD, Dawson LA, Li XA, Das SK, Miften M, Ten Haken RK (2010) Radiation-associated liver injury. Int J Radiat Oncol Biol Phys 76(3 Suppl):S94–S100.  https://doi.org/10.1016/j.ijrobp.2009.06.092 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Dawson LA, Normolle D, Balter JM, McGinn CJ, Lawrence TS, Ten Haken RK (2002) Analysis of radiation-induced liver disease using the Lyman NTCP model. Int J Radiat Oncol Biol Phys 53(4):810–821CrossRefPubMedGoogle Scholar
  15. 15.
    Dawson LA, Ten Haken RK (2005) Partial volume tolerance of the liver to radiation. Semin Radiat Oncol 15(4):279–283.  https://doi.org/10.1016/j.semradonc.2005.04.005 CrossRefPubMedGoogle Scholar
  16. 16.
    Nakahara T, Takagi Y, Takemasa K, Mitsui Y, Tsuyuki A, Shigematsu N, Kubo A (2008) Dose-related fluorodeoxyglucose uptake in acute radiation-induced hepatitis. Eur J Gastroenterol Hepatol 20(10):1040–1044.  https://doi.org/10.1097/MEG.0b013e3282f5f5d5 CrossRefPubMedGoogle Scholar
  17. 17.
    Munden RF, Erasmus JJ, Smythe WR, Madewell JE, Forster KM, Stevens CW (2005) Radiation injury to the liver after intensity-modulated radiation therapy in patients with mesothelioma: an unusual CT appearance. Ajr Am J Roentgenol 184(4):1091–1095.  https://doi.org/10.2214/ajr.184.4.01841091 CrossRefPubMedGoogle Scholar
  18. 18.
    Sempoux C, Horsmans Y, Geubel A, Fraikin J, Van Beers BE, Gigot JF, Lerut J, Rahier J (1997) Severe radiation-induced liver disease following localized radiation therapy for biliopancreatic carcinoma: activation of hepatic stellate cells as an early event. Hepatology 26(1):128–134.  https://doi.org/10.1002/hep.510260117 CrossRefPubMedGoogle Scholar
  19. 19.
    Viswanathan C, Truong MT, Sagebiel TL, Bronstein Y, Vikram R, Patnana M, Silverman PM, Bhosale PR (2014) Abdominal and pelvic complications of nonoperative oncologic therapy. Radiographics 34(4):941–961.  https://doi.org/10.1148/rg.344140082 CrossRefPubMedGoogle Scholar
  20. 20.
    Okamoto D, Nishie A, Asayama Y, Tajima T, Ishigami K, Kakihara D, Nakayama T, Ohga S, Yoshitake T, Shioyama Y, Honda H (2014) Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced MR finding of radiation-induced hepatic injury: relationship to absorbed dose and time course after irradiation. Magn Reson Imaging 32(6):660–664.  https://doi.org/10.1016/j.mri.2014.02.019 CrossRefPubMedGoogle Scholar
  21. 21.
    Luk WH, Au-Yeung AW, Loke TK (2013) Imaging patterns of liver uptakes on PET scan: pearls and pitfalls. Nucl Med Rev Cent East Eur 16(2):75–81.  https://doi.org/10.5603/NMR.2013.0039 CrossRefPubMedGoogle Scholar
  22. 22.
    Noordman BJ, Shapiro J, Spaander MC, Krishnadath KK, van Laarhoven HW, van Berge Henegouwen MI, Nieuwenhuijzen GA, van Hillegersberg R, Sosef MN, Steyerberg EW, Wijnhoven BP, van Lanschot JJ, group Ss (2015) Accuracy of detecting residual disease after cross neoadjuvant chemoradiotherapy for esophageal cancer (preSANO trial): rationale and protocol. JMIR Res Protoc 4(2):e79.  https://doi.org/10.2196/resprot.4320 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Kathiravetpillai N, Koeter M, van der Sangen MJ, Creemers GJ, Luyer MD, Rutten HJ, Nieuwenhuijzen GA (2016) Delaying surgery after neoadjuvant chemoradiotherapy does not significantly influence postoperative morbidity or oncological outcome in patients with oesophageal adenocarcinoma. Eur J Surg Oncol 42(8):1183–1190.  https://doi.org/10.1016/j.ejso.2016.03.033 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Deutschland 2017

Authors and Affiliations

  • Francine E. M. Voncken
    • 1
  • Berthe M. P. Aleman
    • 1
  • Jolanda M. van Dieren
    • 2
  • Cecile Grootscholten
    • 3
  • Ferry Lalezari
    • 4
  • Johanna W. van Sandick
    • 5
  • Jeffrey D. Steinberg
    • 6
  • Erik Vegt
    • 6
  1. 1.Department of Radiation OncologyThe Netherlands Cancer Institute – Antoni van LeeuwenhoekAmsterdamThe Netherlands
  2. 2.Department of GastroenterologyThe Netherlands Cancer Institute – Antoni van LeeuwenhoekAmsterdamThe Netherlands
  3. 3.Department of Internal MedicineThe Netherlands Cancer Institute – Antoni van LeeuwenhoekAmsterdamThe Netherlands
  4. 4.Department of RadiologyThe Netherlands Cancer Institute – Antoni van LeeuwenhoekAmsterdamThe Netherlands
  5. 5.Department of SurgeryThe Netherlands Cancer Institute – Antoni van LeeuwenhoekAmsterdamThe Netherlands
  6. 6.Department of Nuclear MedicineThe Netherlands Cancer Institute – Antoni van LeeuwenhoekAmsterdamThe Netherlands

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