Skip to main content
SpringerLink
Log in

Efficacy of stereotactic body radiotherapy for unresectable or recurrent cholangiocarcinoma: a meta-analysis and systematic review

Wirksamkeit der stereotaktischen Strahlentherapie bei nichtresektablem oder rezidivierendem Cholangiokarzinom: eine Metaanalyse und systematische Übersicht

  • Review Article
  • Published:
Strahlentherapie und Onkologie Aims and scope Submit manuscript

Abstract

Purpose

Non-surgical treatment including stereotactic body radiation therapy (SBRT) have been used practically as alternative modalities for unresectable or recurrent cholangiocarcinoma (CC). We performed a systematic review and meta-analysis to examine the efficacy of SBRT for such patients.

Methods

Embase, PubMed, MEDLINE, and Cochrane library databases were searched systematically until October 2017. Primary endpoint was 1‑year local control (LC) rate; 1‑year overall survival (OS), response rates, and grade ≥3 toxicities were assessed as secondary endpoints.

Results

Eleven studies (226 patients) were included. The prescribed median SBRT dose was 45 (range 30–55) Gy in 3–5 fractions. The pooled 1‑year LC rate was 81.8% (95% confidence interval [CI] 69.4–89.9%) in the studies using an equivalent dose in 2 Gy per fraction (EQD2) ≥71.3 Gy2 and 74.7% (95% CI 57.1–86.7%) in the studies using an EQD2 <71.3 Gy2. The median OS was 13.6 (range 10–35.5) months. The pooled 1‑year OS rate was 53.8% (95% CI 44.9–62.5%) and the pooled 1‑year LC rate was 78.6% (95% CI 69.0–85.8%). Most common toxicity was duodenal ulcer and gastric ulcer in available studies, with the acute incidence of grade ≥3 of less than 10% and the late incidence of 10–20%.

Conclusions

SBRT was a feasible treatment option with respect to achieving a high LC for unresectable or recurrent CC. Gastrointestinal toxicity is acceptable, but remains an obstacle related to dose escalation.

Zusammenfassung

Hintergrund

Die nichtoperative Behandlung einschließlich der stereotaktischen Strahlentherapie (SBRT) wurde praktisch als alternatives Verfahren für das inoperable oder rezidivierende Cholangiokarzinom (CC) eingesetzt. Wir führten eine systematische Überprüfung und Metaanalyse durch, um die Wirksamkeit der SBRT bei solchen Patienten zu untersuchen.

Methoden

Die Embase‑, PubMed‑, Medline- und Cochrane-Bibliotheksdatenbanken wurden bis Oktober 2017 systematisch durchsucht. Primärer Endpunkt war die 1‑Jahres-Rate der lokalen Kontrolle (LC). Das 1‑Jahres-Gesamtüberleben (OS), die Ansprechraten und Toxizitätsgrade >3 wurden als sekundäre Endpunkte bewertet.

Ergebnisse

Elf Studien (226 Patienten) wurden eingeschlossen. Die vorgeschriebene mediane SBRT-Dosis betrug 45 (Bereich 30–55) Gy in 3–5 Fraktionen. Die gepoolte 1‑Jahres-LC-Rate betrug 81,8 % (95 %-Konfidenzintervall [KI] 69,4–89,9 %) in den Studien mit einer äquivalenten Dosis in 2 Gy pro Fraktion (EQD2) ≥71,3 Gy2 und 74,7 % (95 %-KI 57,1–86,7 %) in den Studien mit einer EQD2 <71,3 Gy2. Das mediane OS betrug 13,6 (Bereich 10–35,5) Monate. Die gepoolte 1‑Jahres-OS-Rate betrug 53,8 % (95 %-KI 44,9–62,5 %) und die gepoolte 1‑Jahres-LC-Rate 78,6 % (95 %-KI 69,0–85,8 %). Die häufigsten Toxizitäten waren Ulcus duodeni und Ulcus ventriculi in den verfügbaren Studien mit einer akuten Inzidenz von Grad ≥3 unter 10 % und einer späten Inzidenz von 10 bis 20 %.

Schlussfolgerungen

Die SBRT war eine machbare Behandlungsoption in Bezug auf die Erreichung einer hohen LC bei inoperablen oder rezidivierenden CC. Die gastrointestinale Toxizität ist akzeptabel, bleibt jedoch ein Hindernis im Zusammenhang mit der Dosiseskalation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Alden ME, Mohiuddin M (1994) The impact of radiation dose in combined external beam and intraluminal Ir-192 brachytherapy for bile duct cancer. Int J Radiat Oncol Biol Phys 28:945–951

    Article  CAS  PubMed  Google Scholar 

  2. Barney BM, Olivier KR, Miller RC et al (2012) Clinical outcomes and toxicity using stereotactic body radiotherapy (SBRT) for advanced cholangiocarcinoma. Radiat Oncol 7:67

    Article  PubMed  PubMed Central  Google Scholar 

  3. Ben-Josef E, Normolle D, Ensminger WD et al (2005) Phase II trial of high-dose conformal radiation therapy with concurrent hepatic artery floxuridine for unresectable intrahepatic malignancies. J Clin Oncol 23:8739–8747

    Article  PubMed  Google Scholar 

  4. Benedict SH, Yenice KM, Followill D et al (2010) Stereotactic body radiation therapy: the report of AAPM Task Group 101. Med Phys 37:4078–4101

    Article  PubMed  Google Scholar 

  5. Blettner M, Sauerbrei W, Schlehofer B et al (1999) Traditional reviews, meta-analyses and pooled analyses in epidemiology. Int J Epidemiol 28:1–9

    Article  CAS  PubMed  Google Scholar 

  6. Bujold A, Massey CA, Kim JJ et al (2013) Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma. J Clin Oncol 31:1631–1639

    Article  PubMed  Google Scholar 

  7. Chen Y‑X, Zeng Z‑C, Tang Z‑Y et al (2010) Determining the role of external beam radiotherapy in unresectable intrahepatic cholangiocarcinoma: a retrospective analysis of 84 patients. BMC Cancer 10:492

    Article  PubMed  PubMed Central  Google Scholar 

  8. Cochran WG (1954) The combination of estimates from different experiments. Biometrics 10:101–129

    Article  Google Scholar 

  9. Crane CH, Macdonald KO, Vauthey JN et al (2002) Limitations of conventional doses of chemoradiation for unresectable biliary cancer. Int J Radiat Oncol Biol Phys 53:969–974

    Article  PubMed  Google Scholar 

  10. DerSimonian R, Kacker R (2007) Random-effects model for meta-analysis of clinical trials: an update. Contemp Clin Trials 28:105–114

    Article  PubMed  Google Scholar 

  11. Dewas S, Mirabel X, Kramar A et al (2012) Stereotactic body radiation therapy for liver primary and metastases: the Lille experience. Cancer Radiother 16:58–69

    Article  CAS  PubMed  Google Scholar 

  12. Egger M, Smith GD, Schneider M et al (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Emami B, Lyman J, Brown A et al (1991) Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 21:109–122

    Article  CAS  PubMed  Google Scholar 

  14. Feng M, Suresh K, Schipper MJ et al (2018) Individualized adaptive stereotactic body radiotherapy for liver tumors in patients at high risk for liver damage: a phase 2 clinical trial. Jama Oncol 4:40–47

    Article  PubMed  Google Scholar 

  15. 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 56:908–943

    Article  Google Scholar 

  16. Guckenberger M, Andratschke N, Alheit H et al (2014) Definition of stereotactic body radiotherapy: principles and practice for the treatment of stage I non-small cell lung cancer. Strahlenther Onkol 190:26–33

    Article  CAS  PubMed  Google Scholar 

  17. Guckenberger M, Meyer J, Wilbert J et al (2007) Intra-fractional uncertainties in cone-beam CT based image-guided radiotherapy (IGRT) of pulmonary tumors. Radiother Oncol 83:57–64

    Article  PubMed  Google Scholar 

  18. Guckenberger M, Sweeney RA, Wilbert J et al (2008) Image-guided radiotherapy for liver cancer using respiratory-correlated computed tomography and cone-beam computed tomography. Int J Radiat Oncol Biol Phys 71:297–304

    Article  PubMed  Google Scholar 

  19. Heimbach JK, Gores GJ, Haddock MG et al (2006) Predictors of disease recurrence following neoadjuvant chemoradiotherapy and liver transplantation for unresectable perihilar cholangiocarcinoma. Transplantation 82:1703–1707

    Article  CAS  PubMed  Google Scholar 

  20. Hong TS, Wo JY, Yeap BY et al (2016) Multi-institutional phase II study of high-dose Hypofractionated proton beam therapy in patients with localized, Unresectable Hepatocellular carcinoma and Intrahepatic Cholangiocarcinoma. J Clin Oncol 34:460–468

    Article  CAS  PubMed  Google Scholar 

  21. Ibarra RA, Rojas D, Snyder L et al (2012) Multicenter results of stereotactic body radiotherapy (SBRT) for non-resectable primary liver tumors. Acta Oncol 51:575–583

    Article  PubMed  Google Scholar 

  22. Jung DH, Kim MS, Cho CK et al (2014) Outcomes of stereotactic body radiotherapy for unresectable primary or recurrent cholangiocarcinoma. Radiat Oncol J 32:163–169

    Article  PubMed  PubMed Central  Google Scholar 

  23. Kahaleh M, Mishra R, Shami VM et al (2008) Unresectable Cholangiocarcinoma: comparison of survival in Biliary Stenting alone versus Stenting with Photodynamic therapy. Clin Gastroenterol Hepatol 6:290–297

    Article  PubMed  Google Scholar 

  24. Kang JK, Kim MS, Cho CK et al (2012) Stereotactic body radiation therapy for inoperable hepatocellular carcinoma as a local salvage treatment after incomplete transarterial chemoembolization. Cancer 118:5424–5431

    Article  PubMed  Google Scholar 

  25. Khan SA, Thomas HC, Davidson BR et al (2005) Cholangiocarcinoma. Lancet 366:1303–1314

    Article  PubMed  Google Scholar 

  26. Kim MW, Kim WH, Wang HJ et al (2001) The experiences of hilar skeletonization for the treatment of locally advanced proximal bile duct cancer. Hepatogastroenterology 48:1298–1301

    CAS  PubMed  Google Scholar 

  27. Kopek N, Holt MI, Hansen AT et al (2010) Stereotactic body radiotherapy for unresectable cholangiocarcinoma. Radiother Oncol 94:47–52

    Article  PubMed  Google Scholar 

  28. Lasley FD, Mannina EM, Johnson CS et al (2015) 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 5:e443–e449

    Article  PubMed  Google Scholar 

  29. Liu MY, Lo CH, Lin CS et al (2017) Stereotactic ablative radiotherapy for patients with unresectable or medically inoperable cholangiocarcinoma. Tumori 103:236–241

    Article  PubMed  Google Scholar 

  30. Loveday BPT, Knox JJ, Dawson LA et al (2018) Neoadjuvant hyperfractionated chemoradiation and liver transplantation for unresectable perihilar cholangiocarcinoma in Canada. J Surg Oncol 117:213–219

    Article  CAS  PubMed  Google Scholar 

  31. Mahadevan A, Dagoglu N, Mancias J et al (2015) Stereotactic Body Radiotherapy (SBRT) for Intrahepatic and Hilar Cholangiocarcinoma. J Cancer 6:1099–1104

    Article  PubMed  PubMed Central  Google Scholar 

  32. Mahadevan A, Miksad R, Goldstein M et al (2011) Induction gemcitabine and stereotactic body radiotherapy for locally advanced nonmetastatic pancreas cancer. Int J Radiat Oncol Biol Phys 81:e615–622

    Article  CAS  PubMed  Google Scholar 

  33. Makita C, Nakamura T, Takada A et al (2014) Clinical outcomes and toxicity of proton beam therapy for advanced cholangiocarcinoma. Radiat Oncol 9:26

    Article  PubMed  PubMed Central  Google Scholar 

  34. Mosconi S, Beretta GD, Labianca R et al (2009) Cholangiocarcinoma. Crit Rev Oncol Hematol 69:259–270

    Article  PubMed  Google Scholar 

  35. Patel T (2011) Cholangiocarcinoma—controversies and challenges. Nat Rev Gastroenterol Hepatol 8:189–200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Polistina FA, Guglielmi R, Baiocchi C et al (2011) Chemoradiation treatment with gemcitabine plus stereotactic body radiotherapy for unresectable, non-metastatic, locally advanced hilar cholangiocarcinoma. Results of a five year experience. Radiother Oncol 99:120–123

    Article  CAS  PubMed  Google Scholar 

  37. Potters L, Kavanagh B, Galvin JM et al (2010) American Society for Therapeutic Radiology and Oncology (ASTRO) and American College of Radiology (ACR) practice guideline for the performance of stereotactic body radiation therapy. Int J Radiat Oncol Biol Phys 76:326–332

    Article  PubMed  Google Scholar 

  38. Rea DJ, Heimbach JK, Rosen CB et al (2005) Liver transplantation with neoadjuvant chemoradiation is more effective than resection for hilar cholangiocarcinoma. Ann Surg 242:451–458 (discussion 458–461)

    PubMed  PubMed Central  Google Scholar 

  39. Sandler KA, Veruttipong D, Agopian VG et al (2016) Stereotactic body radiotherapy (SBRT) for locally advanced extrahepatic and intrahepatic cholangiocarcinoma. Adv Radiat Oncol 1:237–243

    Article  PubMed  PubMed Central  Google Scholar 

  40. Scorsetti M, Comito T, Cozzi L et al (2015) The challenge of inoperable hepatocellular carcinoma (HCC): results of a single-institutional experience on stereotactic body radiation therapy (SBRT). J Cancer Res Clin Oncol 141:1301–1309

    Article  CAS  PubMed  Google Scholar 

  41. Shinohara ET, Mitra N, Guo M et al (2008) Radiation therapy is associated with improved survival in the adjuvant and definitive treatment of intrahepatic cholangiocarcinoma. Int J Radiat Oncol Biol Phys 72:1495–1501

    Article  PubMed  Google Scholar 

  42. Sterzing F, Brunner TB, Ernst I et al (2014) Stereotactic body radiotherapy for liver tumors: principles and practical guidelines of the DEGRO Working Group on Stereotactic Radiotherapy. Strahlenther Onkol 190:872–881

    Article  PubMed  Google Scholar 

  43. Stroup DF, Berlin JA, Morton SC et al (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 283:2008–2012

    Article  CAS  PubMed  Google Scholar 

  44. Sumiyoshi T, Shima Y, Okabayashi T et al (2018) Chemoradiotherapy for initially Unresectable locally advanced Cholangiocarcinoma. World J Surg. https://doi.org/10.1007/s00268-018-4558-1

    Article  PubMed  Google Scholar 

  45. Tao R, Krishnan S, Bhosale PR et al (2016) Ablative radiotherapy doses lead to a substantial prolongation of survival in patients with inoperable Intrahepatic Cholangiocarcinoma: a retrospective dose response analysis. J Clin Oncol 34:219–226

    Article  CAS  PubMed  Google Scholar 

  46. Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 92:205–216

    Article  CAS  PubMed  Google Scholar 

  47. Torgeson A, Lloyd S, Boothe D et al (2017) Chemoradiation therapy for Unresected Extrahepatic Cholangiocarcinoma: a propensity score-matched analysis. Ann Surg Oncol 24:4001–4008

    Article  PubMed  Google Scholar 

  48. Torre LA, Bray F, Siegel RL et al (2015) Global cancer statistics, 2012. Ca Cancer J Clin 65:87–108

    Article  PubMed  Google Scholar 

  49. Tse RV, Hawkins M, Lockwood G et al (2008) Phase I study of individualized stereotactic body radiotherapy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Clin Oncol 26:657–664

    Article  PubMed  Google Scholar 

  50. Weiner AA, Olsen J, Ma D et al (2016) Stereotactic body radiotherapy for primary hepatic malignancies—Report of a phase I/II institutional study. Radiother Oncol 121:79–85

    Article  PubMed  PubMed Central  Google Scholar 

  51. Wells GSB, O’connell D, Peterson J, Welch V, Losos M (2009) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Hospital Research Institute, Oxford, Ottawa

    Google Scholar 

  52. Xu Q, Hanna G, Grimm J et al (2014) Quantifying rigid and nonrigid motion of liver tumors during stereotactic body radiation therapy. Int J Radiat Oncol Biol Phys 90:94–101

    Article  PubMed  Google Scholar 

  53. Zeng ZC, Tang ZY, Fan J et al (2006) Consideration of the role of radiotherapy for unresectable intrahepatic cholangiocarcinoma: a retrospective analysis of 75 patients. Cancer J 12:113–122

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Korea (Republic of)

    Jeongshim Lee MD & Woong Sub Koom MD, PhD

  2. Department of Radiation Oncology, Inha University Hospital, Incheon, Korea (Republic of)

    Jeongshim Lee MD

  3. Department of Radiation Oncology, Korea University Ansan Hospital, 123 Jeokgeum-ro, Danwon-gu, 15355, Ansan, Gyeonggi-do, Korea (Republic of)

    Won Sup Yoon MD, PhD & Chai Hong Rim MD

Authors
  1. Jeongshim Lee MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Won Sup Yoon MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Woong Sub Koom MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chai Hong Rim MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chai Hong Rim MD.

Ethics declarations

Conflict of interest

J. Lee, W.S. Yoon, W.S. Koom and C.H. Rim declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, J., Yoon, W.S., Koom, W.S. et al. Efficacy of stereotactic body radiotherapy for unresectable or recurrent cholangiocarcinoma: a meta-analysis and systematic review. Strahlenther Onkol 195, 93–102 (2019). https://doi.org/10.1007/s00066-018-1367-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00066-018-1367-2

Keywords

Schlüsselwörter

Search

Navigation