Protocol for the STRONG trial: stereotactic body radiation therapy following chemotherapy for unresectable perihilar cholangiocarcinoma, a phase I feasibility study

Merel S Koedijk, Ben J M Heijmen, Bas Groot Koerkamp, Ferry A L M Eskens, Dave Sprengers, Jan-Werner Poley, Dik C van Gent, Luc J W van der Laan, Bronno van der Holt, François E J A Willemssen, Alejandra Méndez Romero, Merel S Koedijk, Ben J M Heijmen, Bas Groot Koerkamp, Ferry A L M Eskens, Dave Sprengers, Jan-Werner Poley, Dik C van Gent, Luc J W van der Laan, Bronno van der Holt, François E J A Willemssen, Alejandra Méndez Romero

Abstract

Introduction: For patients with perihilar cholangiocarcinoma (CCA), surgery is the only treatment modality that can result in cure. Unfortunately, in the majority of these patients, the tumours are found to be unresectable at presentation due to either local invasive tumour growth or the presence of distant metastases. For patients with unresectable CCA, palliative chemotherapy is the standard treatment yielding an estimated median overall survival (OS) of 12-15.2 months. There is no evidence from randomised trials to support the use of stereotactic body radiation therapy (SBRT) for CCA. However, small and most often retrospective studies combining chemotherapy with SBRT have shown promising results with OS reaching up to 33-35 months.

Methods and analysis: This study has been designed as a single-centre phase I feasibility trial and will investigate the addition of SBRT after standard chemotherapy in patients with unresectable perihilar CCA (T1-4 N0-1 M0). A total of six patients will be included. SBRT will be delivered in 15 fractions of 3-4.5 Gy (risk adapted). The primary objective of this study is to determine feasibility and toxicity. Secondary outcomes include local tumour control, progression-free survival (PFS), OS and quality of life. Length of follow-up will be 2 years. As an ancillary study, the personalised effects of radiotherapy will be measured in vitro, in patient-derived tumour and bile duct organoid cultures.

Ethics and dissemination: Ethics approval for the STRONG trial has been granted by the Medical Ethics Committee of Erasmus MC Rotterdam, the Netherlands. It is estimated that all patients will be included between October 2017 and October 2018. The results of this study will be published in a peer-reviewed journal, and presented at national and international conferences.

Trial registration number: NCT03307538; Pre-results.

Keywords: klatskin tumour; perihilar cholangiocarcinoma; stereotactic body radiation oncology.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Study outline. SBRT, stereotactic body radiation therapy.

References

    1. Aitken KL, Hawkins MA. The role of radiotherapy and chemoradiation in the management of primary liver tumours. Clin Oncol 2014;26:569–80. 10.1016/j.clon.2014.05.016
    1. Shinohara ET, Mitra N, Guo M, et al. . Radiotherapy is associated with improved survival in adjuvant and palliative treatment of extrahepatic cholangiocarcinomas. Int J Radiat Oncol Biol Phys 2009;74:1191–8. 10.1016/j.ijrobp.2008.09.017
    1. Weiss MJ, Cosgrove D, Herman JM, et al. . Multimodal treatment strategies for advanced hilar cholangiocarcinoma. Langenbecks Arch Surg 2014;399:679–92. 10.1007/s00423-014-1219-1
    1. Mansour JC, Aloia TA, Crane CH, et al. . Hilar cholangiocarcinoma: expert consensus statement. HPB 2015;17:691–9. 10.1111/hpb.12450
    1. Blechacz B. Cholangiocarcinoma: Current Knowledge and New Developments. Gut Liver 2017;11:13–26. 10.5009/gnl15568
    1. Valle J, Wasan H, Palmer DH, et al. . Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 2010;362:1273–81. 10.1056/NEJMoa0908721
    1. Eckmann KR, Patel DK, Landgraf A, et al. . Chemotherapy outcomes for the treatment of unresectable intrahepatic and hilar cholangiocarcinoma: a retrospective analysis. Gastrointest Cancer Res 2011;4(5-6):155–60.
    1. Coelen RJS, Vogel JA, Vroomen L, et al. . Ablation with irreversible electroporation in patients with advanced perihilar cholangiocarcinoma (ALPACA): a multicentre phase I/II feasibility study protocol. BMJ Open 2017;7:e015810 10.1136/bmjopen-2016-015810
    1. Melenhorst MC, Scheffer HJ, Vroomen LG, et al. . Percutaneous Irreversible Electroporation of Unresectable Hilar Cholangiocarcinoma (Klatskin Tumor): A Case Report. Cardiovasc Intervent Radiol 2016;39:117–21. 10.1007/s00270-015-1126-z
    1. Wu TT, Li WM, Li HC, et al. . Percutaneous intraductal radiofrequency ablation for extrahepatic distal cholangiocarcinoma: A method for prolonging stent patency and achieving better functional status and quality of life. Cardiovasc Intervent Radiol 2017;40:260–9. 10.1007/s00270-016-1483-2
    1. Wagner A, Denzer UW, Neureiter D, et al. . Temoporfin improves efficacy of photodynamic therapy in advanced biliary tract carcinoma: A multicenter prospective phase II study. Hepatology 2015;62:1456–65. 10.1002/hep.27905
    1. Mattiucci GC, Autorino R, Tringali A, et al. . A Phase I study of high-dose-rate intraluminal brachytherapy as palliative treatment in extrahepatic biliary tract cancer. Brachytherapy 2015;14:401–4. 10.1016/j.brachy.2014.12.002
    1. Mahadevan A, Dagoglu N, Mancias J, et al. . Stereotactic Body Radiotherapy (SBRT) for Intrahepatic and Hilar Cholangiocarcinoma. J Cancer 2015;6:1099–104. 10.7150/jca.13032
    1. Kopek N, Holt MI, Hansen AT, et al. . Stereotactic body radiotherapy for unresectable cholangiocarcinoma. Radiother Oncol 2010;94:47–52. 10.1016/j.radonc.2009.11.004
    1. Tse RV, Hawkins M, Lockwood G, et al. . Phase I study of individualized stereotactic body radiotherapy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Clin Oncol 2008;26:657–64. 10.1200/JCO.2007.14.3529
    1. Polistina FA, Guglielmi R, Baiocchi C, et al. . Chemoradiation treatment with gemcitabine plus stereotactic body radiotherapy for unresectable, non-metastatic, locally advanced hilar cholangiocarcinoma. Results of a five year experience. Radiother Oncol 2011;99:120–3. 10.1016/j.radonc.2011.05.016
    1. Barney BM, Olivier KR, Miller RC, et al. . Clinical outcomes and toxicity using stereotactic body radiotherapy (SBRT) for advanced cholangiocarcinoma. Radiat Oncol 2012;7:67 10.1186/1748-717X-7-67
    1. Momm F, Schubert E, Henne K, et al. . Stereotactic fractionated radiotherapy for Klatskin tumours. Radiother Oncol 2010;95:99–102. 10.1016/j.radonc.2010.03.013
    1. Jung DH, Kim MS, Cho CK, et al. . Outcomes of stereotactic body radiotherapy for unresectable primary or recurrent cholangiocarcinoma. Radiat Oncol J 2014;32:163–9. 10.3857/roj.2014.32.3.163
    1. Tao R, Krishnan S, Bhosale PR, et al. . Ablative radiotherapy doses lead to a substantial prolongation of survival in patients with inoperable intrahepatic cholangiocarcinoma: a retrospective dose response analysis. J Clin Oncol 2016;34:219–26. 10.1200/JCO.2015.61.3778
    1. Sandler KA, Veruttipong D, Agopian VG, et al. . Stereotactic body radiotherapy (SBRT) for locally advanced extrahepatic and intrahepatic cholangiocarcinoma. Adv Radiat Oncol 2016;1:237–43. 10.1016/j.adro.2016.10.008
    1. Eisenhauer EA, Therasse P, Bogaerts J, et al. . New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228–47. 10.1016/j.ejca.2008.10.026
    1. Huch M, Gehart H, van Boxtel R, et al. . Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell 2015;160:299–312. 10.1016/j.cell.2014.11.050
    1. Blokzijl F, de Ligt J, Jager M, et al. . Tissue-specific mutation accumulation in human adult stem cells during life. Nature 2016;538:260–4. 10.1038/nature19768
    1. Welling TH, Feng M, Wan S, et al. . Neoadjuvant stereotactic body radiation therapy, capecitabine, and liver transplantation for unresectable hilar cholangiocarcinoma. Liver Transpl 2014;20:81–8. 10.1002/lt.23757
    1. Schefter TE, Kavanagh BD, Timmerman RD, et al. . A phase I trial of stereotactic body radiation therapy (SBRT) for liver metastases. Int J Radiat Oncol Biol Phys 2005;62:1371–8. 10.1016/j.ijrobp.2005.01.002
    1. Dawson LA, Eccles C, Craig T. Individualized image guided iso-NTCP based liver cancer SBRT. Acta Oncol 2006;45:856–64. 10.1080/02841860600936369
    1. Son SH, Choi BO, Ryu MR, et al. . Stereotactic body radiotherapy for patients with unresectable primary hepatocellular carcinoma: dose-volumetric parameters predicting the hepatic complication. Int J Radiat Oncol Biol Phys 2010;78:1073–80. 10.1016/j.ijrobp.2009.09.009
    1. Kavanagh BD, Pan CC, Dawson LA, et al. . Radiation dose-volume effects in the stomach and small bowel. Int J Radiat Oncol Biol Phys 2010;76(3 Suppl):S101–7. 10.1016/j.ijrobp.2009.05.071
    1. Kong FM, Ritter T, Quint DJ, et al. . Consideration of dose limits for organs at risk of thoracic radiotherapy: atlas for lung, proximal bronchial tree, esophagus, spinal cord, ribs, and brachial plexus. Int J Radiat Oncol Biol Phys 2011;81:1442–57. 10.1016/j.ijrobp.2010.07.1977
    1. Toesca DA, Osmundson EC, Eyben RV, et al. . Central liver toxicity after SBRT: An expanded analysis and predictive nomogram. Radiother Oncol 2017;122:130–6. 10.1016/j.radonc.2016.10.024

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться