Top

Published in:

Open Access 01-12-2016 | Original research

Yttrium-90 radioembolization for colorectal cancer liver metastases: a prospective cohort study on circulating angiogenic factors and treatment response

Authors: C. E. N. M. Rosenbaum, A. F. van den Hoven, M. N. G. J. A. Braat, M. Koopman, M. G. E. H. Lam, B. A. Zonnenberg, H. M. Verkooijen, M. A. A. J. van den Bosch

Published in: EJNMMI Research | Issue 1/2016

Abstract

Background

Yttrium-90 radioembolization (⁹⁰Y-RE) as a treatment for liver tumours induces radiation damage and hypoxia in liver tissue, which is also a trigger for systemic release of angiogenic factors, potentially stimulating tumour growth. We examined changes in circulating angiogenic factors following ⁹⁰Y-RE and investigated the association between response and angiogenic factors. In this prospective study, 42 patients with unresectable, chemorefractory metastatic colorectal cancer (CRCLM) were treated with ⁹⁰Y-RE. Blood samples were collected pre-treatment and at 0, 1, 3, 7 and 30 days of follow-up. Response was measured with MRI according to RECIST 1.1 at 1 month and subsequently 3-month interval until progressive disease (PD) occurred. Associations between circulating angiogenic factors and response were examined with linear mixed model analysis.

Results

Following ⁹⁰Y-RE, three angiogenic factors demonstrated an increase in plasma levels, i.e., vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and angiopoietin-2 (Ang-2). Non-responders (= PD at 1-month follow-up, n = 10) had a significant increase of Ang-2 and HGF at 3 and 7 days post treatment compared to responders (= stable disease or better, n = 32), who showed little to no changes in plasma levels (respectively p = 0.01 and p = 0.007). Median overall survival was 9.2 months (95% confidence interval 6.1–12.4).

Conclusions

Significant increases in plasma levels of Ang-2 and HGF in the first week after treatment were associated with rapid progressive disease of liver lesions at 1 month after ⁹⁰Y-RE. Combination of ⁹⁰Y-RE with anti-angiogenic therapy may reduce these effects and result in better response.

Gray B, Van Hazel GA, Hope M, et al. Randomised trial of SIR-Spheres® plus chemotherapy vs. chemotherapy alone for treating patients with liver metastases from primary large bowel cancer. Ann Oncol. 2001;12:1711–20. doi:10.1002/jso.20141.CrossRefPubMed

Hendlisz A, Eynde MV, Peeters M, et al. Phase III trial comparing protracted intravenous fluorouracil infusion alone or with yttrium-90 resin microspheres radioembolization for liver-limited metastatic colorectal cancer refractory to standard chemotherapy. J Clin Oncol. 2010;28:3687–94. doi:10.1200/JCO.2010.28.5643.CrossRefPubMed

Van Hazel G, Blackwell A, Anderson J, et al. Randomised phase 2 trial of SIR-Spheres® plus fluorouracil/leucovorin chemotherapy versus fluorouracil/leucovorin chemotherapy alone in advanced colorectal cancer. J Surg Oncol. 2004;88:78–85. doi:10.1002/jso.20141.CrossRefPubMed

Kennedy AS, Coldwell D, Nutting C, et al. Resin 90Y-microsphere brachytherapy for unresectable colorectal liver metastases: modern USA experience. Int J Radiat Oncol Biol Phys. 2006;65:412–25. doi:10.1016/j.ijrobp.2005.12.051.CrossRefPubMed

Vente MA, Wondergem M, van der Tweel I, et al. Yttrium-90 microsphere radioembolization for the treatment of liver malignancies: a structured meta-analysis. Eur Radiol. 2009;19(4):951–9. doi:10.1007/s00330-008-1211-7.CrossRefPubMed

Scheer MG, Stollman TH, Vogel WV, Boerman OC, Oyen WJ, Ruers TJ. Increased metabolic activity of indolent liver metastases after resection of a primary colorectal tumor. J Nucl Med. 2008;49(6):887–91. doi:10.2967/jnumed.107.048371.CrossRefPubMed

Venderbosch S, de Wilt JH, Teerenstra S, et al. Prognostic value of resection of primary tumor in patients with stage IV colorectal cancer: retrospective analysis of two randomized studies and a review of the literature. Ann Surg Oncol. 2011;18(12):3252–60. doi:10.1245/s10434-011-1951-5.CrossRefPubMedPubMedCentral

Li XFGS, Zheng CS, Zhuo CK, Liu X. Expression of plasma vascular endothelial growth factor in patients with hepatocellular carcinoma and effect of transcatheter arterial chemoembolization therapy on plasma vascular endothelial growth factor level. World J Gastroenterol. 2004;10:2878–82. doi:10.3748/wjg.v10.i19.2878.CrossRefPubMedPubMedCentral

Suzuki HMM, Kawaguchi C, Adachi M, Miura S, Ishii H. Serum vascular endothelial growth factor in the course of transcatheter arterial embolization of hepatocellular carcinoma. Int J Oncol. 1999;14:1087–90. doi:10.3892/ijo.14.6.1087.PubMed

10.

Sergio A, Cristofori C, Cardin R, et al. Transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): the role of angiogenesis and invasiveness. Am J Gastroenterol. 2008;103(4):914–21. doi:10.1111/j.1572-0241.2007.01712.x.CrossRefPubMed

11.

Rosenbaum CE, Verkooijen HM, Lam MG, et al. Radioembolization for treatment of salvage patients with colorectal cancer liver metastases: a systematic review. J Nucl Med. 2013;54(11):1890–5. doi:10.2967/jnumed.113.119545.CrossRefPubMed

12.

Dvorak HF. Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol. 2002;20(21):4368–80. doi:10.1200/JCO.2002.10.088.CrossRefPubMed

13.

Rahbari NN, Reissfelder C, Muhlbayer M, et al. Correlation of circulating angiogenic factors with circulating tumor cells and disease recurrence in patients undergoing curative resection for colorectal liver metastases. Ann Surg Oncol. 2011;18(8):2182–91. doi:10.1245/s10434-011-1761-9.CrossRefPubMed

14.

Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature. 2000;407:249–57. doi:10.1038/nrd3455.CrossRefPubMed

15.

Giammarile F, Bodei L, Chiesa C, et al. EANM procedure guideline for the treatment of liver cancer and liver metastases with intra-arterial radioactive compounds. Eur J Nucl Med Mol Imaging. 2011;38:1393–406. doi:10.1007/s00259-011-1812-2.CrossRefPubMed

16.

Salem R, Thurston KG. Radioembolization with yttrium-90 microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies: part 3: comprehensive literature review and future direction. J Vasc Interv Radiol. 2006;17:1571–93. doi:10.1097/01.RVI.0000236744.34720.73.CrossRefPubMed

17.

Salem R, Thurston KG. Radioembolization with 90yttrium microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies. Part 2: special topics. J Vasc Interv Radiol. 2006;17:1425–39. doi:10.1097/01.RVI.0000235779.88652.53.CrossRefPubMed

18.

Salem R, Thurston KG. Radioembolization with 90Yttrium microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies. Part 1: Technical and methodologic considerations. J Vasc Interv Radiol. 2006;17:1251–78. doi:10.1097/01.RVI.0000233785.75257.9A.CrossRefPubMed

19.

de Jager W, Hoppenreijs EP, Wulffraat NM, Wedderburn LR, Kuis W, Prakken BJ. Blood and synovial fluid cytokine signatures in patients with juvenile idiopathic arthritis: a cross-sectional study. Ann Rheum Dis. 2007;66(5):589–98. doi:10.1136/ard.2006.061853.CrossRefPubMed

20.

De Jager W, Prakken BJ, Bijlsma JW, Kuis W, Rijkers GT. Improved multiplex immunoassay performance in human plasma and synovial fluid following removal of interfering heterophilic antibodies. J Immunol Methods. 2005;300:124–35. doi:10.1016/j.jim.2005.03.009.CrossRefPubMed

21.

Bester L, Meteling B, Pocock N, et al. Radioembolization versus standard care of hepatic metastases: comparative retrospective cohort study of survival outcomes and adverse events in salvage patients. J Vasc Interv Radiol. 2012;23:96–105. doi:10.1016/j.jvir.2011.09.028.CrossRefPubMed

22.

Lim L, Gibbs P, Yip D, et al. Prospective study of treatment with selective internal radiation therapy spheres in patients with unresectable primary or secondary hepatic malignancies. Intern Med J. 2005;35:222–7. doi:10.1186/1471-2407-5-132.CrossRefPubMed

23.

Seidensticker R, Denecke T, Kraus P, et al. Matched-pair comparison of radioembolization plus best supportive care versus best supportive care alone for chemotherapy refractory liver-dominant colorectal metastases. Cardiovasc Intervent Radiol. 2012;35:1066–73. doi:10.1007/s00270-011-0234-7.CrossRefPubMed

24.

Martin LK, Cucci A, Wei L, et al. Yttrium-90 radioembolization as salvage therapy for colorectal cancer with liver metastases. Clin Colorectal Cancer. 2012;11:195–9. doi:10.1016/j.clcc.2011.12.002.CrossRefPubMed

25.

Fahmueller YN, Nagel D, Hoffmann RT, et al. Predictive and prognostic value of circulating nucleosomes and serum biomarkers in patients with metastasized colorectal cancer undergoing Selective Internal Radiation Therapy. BMC Cancer. 2012;12:5. doi:10.1186/1471-2407-12-5.CrossRefPubMedPubMedCentral

26.

Shim JH, Park JW, Kim JH, et al. Association between increment of serum VEGF level and prognosis after transcatheter arterial chemoembolization in hepatocellular carcinoma patients. Cancer Sci. 2008;99(10):2037–44. doi:10.1111/j.1349-7006.2008.00909.x.PubMed

27.

Korse CM, Bonfrer JM, Prevoo W, Baas P, Taal BG. Increase of angiogenic growth factors after hepatic artery embolization in patients with neuroendocrine tumours. Tumour Biol. 2011;32(4):647–52. doi:10.1007/s13277-011-0164-7.CrossRefPubMed

28.

Carpizo DR, Gensure RH, Yu X, et al. Pilot study of angiogenic response to yttrium-90 radioembolization with resin microspheres. J Vasc Interv Radiol. 2014;25(2):297–306.e291. doi:10.1016/j.jvir.2013.10.030.CrossRefPubMed

29.

Gorski DHBM, Jaskowiak NT, Calvin DP, Mauceri HJ, Salloum RM, Seetharam S, Koons A, Hari DM, Kufe DW, Weichselbaum RR. Blockade of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation. Cancer Res. 1999;59:3374–8.PubMed

30.

Gibbs P, Heinemann V, Findlay MPN, et al. SIRFLOX: Randomized phase III trial bevacizumab (bev) versus mFOLFOX6 + selective internal radiation therapy (SIRT) in patients with metastatic colorectal cancer (mCRC). J Clin Oncol. 2015;33(suppl):abstract 3502. doi:10.1200/JCO.2015.66.1181.

Title: Yttrium-90 radioembolization for colorectal cancer liver metastases: a prospective cohort study on circulating angiogenic factors and treatment response
Authors: C. E. N. M. Rosenbaum
A. F. van den Hoven
M. N. G. J. A. Braat
M. Koopman
M. G. E. H. Lam
B. A. Zonnenberg
H. M. Verkooijen
M. A. A. J. van den Bosch
Publication date: 01-12-2016
Publisher: Springer Berlin Heidelberg
Published in: EJNMMI Research / Issue 1/2016
Electronic ISSN: 2191-219X
DOI: https://doi.org/10.1186/s13550-016-0236-1

At a glance: The STEP trials

Springer Medicine

Yttrium-90 radioembolization for colorectal cancer liver metastases: a prospective cohort study on circulating angiogenic factors and treatment response

Abstract

Background

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2016

Erratum to: Absorption, distribution and excretion of intravenously injected 68Ge/68Ga generator eluate in healthy rats, and estimation of human radiation dosimetry

Predictive factors of 18F-choline PET/CT positivity in patients with prostate cancer recurrence after radiation therapy: is the impact of PSA nadir underestimated?

[18F]tetrafluoroborate as a PET tracer for the sodium/iodide symporter: the importance of specific activity

Improved safety and efficacy of 213Bi-DOTATATE-targeted alpha therapy of somatostatin receptor-expressing neuroendocrine tumors in mice pre-treated with l-lysine

Comparison of the image-derived radioactivity and blood-sample radioactivity for estimating the clinical indicators of the efficacy of boron neutron capture therapy (BNCT): 4-borono-2-18F-fluoro-phenylalanine (FBPA) PET study

Impact of 68Ga-PSMA PET/CT on salvage radiotherapy planning in patients with prostate cancer and persisting PSA values or biochemical relapse after prostatectomy