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CardioVascular and Interventional Radiology

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01-04-2012 | Clinical Investigation

Radioembolization of Symptomatic, Unresectable Neuroendocrine Hepatic Metastases Using Yttrium-90 Microspheres

Authors: Philipp M. Paprottka, Ralf-T. Hoffmann, Alexander Haug, Wieland H. Sommer, Franziska Raeßler, Christoph G. Trumm, Gerwin P. Schmidt, Nima Ashoori, Maximilian F. Reiser, Tobias F. Jakobs

Published in: CardioVascular and Interventional Radiology | Issue 2/2012

Abstract

Purpose

To evaluate safety, efficacy, and symptom-control of radioembolization in patients with unresectable liver metastases from neuroendocrine tumors (NETLMs).

Materials and Methods

Forty-two patients (mean age of 62 years) with treatment-refractory NETLMs underwent radioembolization using yttrium-90 (⁹⁰Y) resin microspheres. Posttreatment tumor response was assessed by cross-sectional imaging using the Response Evaluation Criteria in Solid Tumors (RECIST) and tumor-marker levels. Laboratory and clinical toxicities and clinical symptoms were monitored.

Results

The median activity delivered was 1.63 GBq (range 0.63–2.36). Imaging follow-up using RECIST at 3-month follow-up demonstrated partial response, stable disease, and progressive disease in 22.5, 75.0, and 2.5% of patients, respectively. In 97.5% of patients, the liver lesions appeared hypovascular or partially necrotic. The mean follow-up was 16.2 months with 40 patients (95.2%) remaining alive. The median decrease in tumor-marker levels at 3 months was 54.8% (chromogranin A) and 37.3% (serotonin), respectively. There were no acute or delayed toxicities greater than grade 2 according to Common Terminology Criteria for Adverse Events [CTCAE (v3.0)]. No radiation-induced liver disease was noted. Improvement of clinical symptoms 3 months after treatment was observed in 36 of 38 symptomatic patients.

Conclusion

Radioembolization with ⁹⁰Y-microspheres is a safe and effective treatment option in patients with otherwise treatment-refractory NETLMs. Antitumoral effect is supported by good local tumor control, decreased tumor-marker levels, and improved clinical symptoms. Further investigation is warranted to define the role of radioembolization in the treatment paradigm for NETLMs.

Abrams RA, King D, Wilson JF (1987) Objective response of malignant carcinoid to radiation therapy. Int J Radiat Oncol Biol Physiol 13(6):869–873CrossRef

Akerstrom G, Hellman P, Hessman O, Osmak L (2005) Management of midgut carcinoids. J Surg Oncol 89(3):161–169PubMedCrossRef

Brown KT, Koh BY, Brody LA et al (1999) Particle embolization of hepatic neuroendocrine metastases for control of pain and hormonal symptoms. J Vasc Interv Radiol 10(4):397–403PubMedCrossRef

Cao CQ, Yan TD, Bester L, Liauw W, Morris DL (2010) Radioembolization with yttrium microspheres for neuroendocrine tumour liver metastases. Br J Surg 97(4):537–543PubMedCrossRef

Capurso G, Bettini R, Rinzivillo M, Boninsegna L, Delle Fave G, Falconi M (2011) Role of resection of the primary pancreatic neuroendocrine tumour only in patients with unresectable metastatic liver disease: a systematic review. Neuroendocrinology. doi:10.1159/000324770

Carr BI (2004) Hepatic arterial ⁹⁰Yttrium glass microspheres (Therasphere) for unresectable hepatocellular carcinoma: interim safety and survival data on 65 patients. Liver Transpl 10(2 Suppl 1):S107–S110

Chakravarthy A, Abrams RA (1995) Radiation therapy in the management of patients with malignant carcinoid tumors. Cancer 75(6):1386–1390PubMedCrossRef

Chamberlain RS, Canes D, Brown KT et al (2000) Hepatic neuroendocrine metastases: does intervention alter outcomes? J Am Coll Surg 190(4):432–445PubMedCrossRef

Chen H, Hardacre JM, Uzar A, Cameron JL, Choti MA (1998) Isolated liver metastases from neuroendocrine tumors: does resection prolong survival? J Am Coll Surg 187(1):88–92; discussion 92–93

10.

Coldwell DM, Sewell PE (2005) The expanding role of interventional radiology in the supportive care of the oncology patient: from diagnosis to therapy. Semin Oncol 32(2):169–173PubMedCrossRef

11.

Delcore R, Friesen SR (1994) Gastrointestinal neuroendocrine tumors. J Am Coll Surg 178(2):187–211PubMed

12.

Duffaud F, Therasse P (2000) New guidelines to evaluate the response to treatment in solid tumors. Bull Cancer 87(12):881–886PubMed

13.

Eriksson BK, Larsson EG, Skogseid BM, Lofberg AM, Lorelius LE, Oberg KE (1998) Liver embolizations of patients with malignant neuroendocrine gastrointestinal tumors. Cancer 83(11):2293–2301PubMedCrossRef

14.

Gaitan-Gaitan A, Rider WD, Bush RS (1975) Carcinoid tumor-cure by irradiation. Int J Radiat Oncol Biol Physiol 1(1–2):9–13CrossRef

15.

Gray B, Van Hazel G, Hope M et al (2001) Randomised trial of SIR-Spheres plus chemotherapy vs. chemotherapy alone for treating patients with liver metastases from primary large bowel cancer. Ann Oncol 12(12):1711–1720PubMedCrossRef

16.

Gupta S, Johnson MM, Murthy R et al (2005) Hepatic arterial embolization and chemoembolization for the treatment of patients with metastatic neuroendocrine tumors: variables affecting response rates and survival. Cancer 104(8):1590–1602PubMedCrossRef

17.

Hibi T, Sano T, Sakamoto Y et al (2007) Surgery for hepatic neuroendocrine tumors: a single institutional experience in Japan. Jpn J Clin Oncol 37(2):102–107PubMedCrossRef

18.

Jakobs TF, Hoffmann RT, Tatsch K, Trumm C, Reiser MF, Helmberger TK (2007) Developments and perspectives in radioablative techniques. Radiologe 47(12):1083–1088PubMedCrossRef

19.

Jakobs TF, Hoffmann RT, Tatsch K, Trumm C, Reiser MF (2008) Therapy response of liver tumors after selective internal radiation therapy. Radiologe 48(9):839–849PubMedCrossRef

20.

Keane TJ, Rider WD, Harwood AR, Thomas GM, Cummings BJ (1981) Whole abdominal radiation in the management of metastatic gastrointestinal carcinoid tumor. Int J Radiat Oncol Biol Physiol 7(11):1519–1521CrossRef

21.

Kennedy A, Nag S, Salem R et al (2007) Recommendations for radioembolization of hepatic malignancies using yttrium-90 microsphere brachytherapy: a consensus panel report from the radioembolization Brachytherapy Oncology Consortium. Int J Radiat Oncol Biol Physiol 68(1):13–23CrossRef

22.

Kennedy AS, Dezarn WA, McNeillie P et al (2008) Radioembolization for unresectable neuroendocrine hepatic metastases using resin 90Y-microspheres: early results in 148 patients. Am J Clin Oncol 31(3):271–279PubMedCrossRef

23.

King J, Quinn R, Glenn DM et al (2008) Radioembolization with selective internal radiation microspheres for neuroendocrine liver metastases. Cancer 113(5):921–929PubMedCrossRef

24.

Kress O, Wagner HJ, Wied M, Klose KJ, Arnold R, Alfke H (2003) Transarterial chemoembolization of advanced liver metastases of neuroendocrine tumors―a retrospective single-center analysis. Digestion 68(2–3):94–101PubMedCrossRef

25.

Madoff DC, Gupta S, Ahrar K, Murthy R, Yao JC (2006) Update on the management of neuroendocrine hepatic metastases. J Vasc Interv Radiol 17(8):1235–1249; quiz 1250

26.

McStay MK, Maudgil D, Williams M et al (2005) Large-volume liver metastases from neuroendocrine tumors: hepatic intraarterial 90Y-DOTA-lanreotide as effective palliative therapy. Radiology 237(2):718–726PubMedCrossRef

27.

Modlin IM, Sandor A (1997) An analysis of 8305 cases of carcinoid tumors. Cancer 79(4):813–829PubMedCrossRef

28.

Modlin IM, Kidd M, Latich I, Zikusoka MN, Shapiro MD (2005) Current status of gastrointestinal carcinoids. Gastroenterology 128(6):1717–1751PubMedCrossRef

29.

Moertel CG, Johnson CM, McKusick MA et al (1994) The management of patients with advanced carcinoid tumors and islet cell carcinomas. Ann Intern Med 120(4):302–309PubMed

30.

Murthy R, Nunez R, Szklaruk J et al (2005) Yttrium-90 microsphere therapy for hepatic malignancy: devices, indications, technical considerations, and potential complications. Radiographics 25(Suppl 1):S41–S55PubMedCrossRef

31.

Musunuru S, Chen H, Rajpal S et al (2006) Metastatic neuroendocrine hepatic tumors: resection improves survival. Arch Surg 141(10):1000–1004; discussion 1005

32.

Nave H, Mossinger E, Feist H, Lang H, Raab H (2001) Surgery as primary treatment in patients with liver metastases from carcinoid tumors: a retrospective, unicentric study over 13 years. Surgery 129(2):170–175PubMedCrossRef

33.

Norton JA (2005) Endocrine tumours of the gastrointestinal tract. Surgical treatment of neuroendocrine metastases. Best Pract Res Clin Gastroenterol 19(4):577–583PubMedCrossRef

34.

Norton JA, Kerlan RK (2003) Hepatic artery embolization for treatment of patients with metastatic carcinoid tumors: a commentary. Cancer J 9(4):241–243PubMedCrossRef

35.

Oberg K (1999) Neuroendocrine gastrointestinal tumors—a condensed overview of diagnosis and treatment. Ann Oncol 10(Suppl 2):S3–S8PubMedCrossRef

36.

Oberg K (2002) Carcinoid tumors: molecular genetics, tumor biology, and update of diagnosis and treatment. Curr Opin Oncol 14(1):38–45PubMedCrossRef

37.

Osborne DA, Zervos EE, Strosberg J et al (2006) Improved outcome with cytoreduction versus embolization for symptomatic hepatic metastases of carcinoid and neuroendocrine tumors. Ann Surg Oncol 13(4):572–581PubMedCrossRef

38.

Paprottka PM, Jakobs TF, Reiser MF, Hoffmann RT (2011) Practical vascular anatomy in the preparation of radioembolization. Cardiovasc Interv Radiol 34:287–294CrossRef

39.

Que FG, Nagorney DM, Batts KP, Linz LJ, Kvols LK (1995) Hepatic resection for metastatic neuroendocrine carcinomas. Am J Surg 169(1):36–42; discussion 42–33

40.

Reddy PS, Burroughs KD, Hales LM et al (2007) Seneca Valley virus, a systemically deliverable oncolytic picornavirus, and the treatment of neuroendocrine cancers. J Natl Cancer Inst 99(21):1623–1633PubMedCrossRef

41.

Ruszniewski P, Malka D (2000) Hepatic arterial chemoembolization in the management of advanced digestive endocrine tumors. Digestion 62(Suppl 1):79–83PubMedCrossRef

42.

Safford SD, Coleman RE, Gockerman JP et al (2004) Iodine-131 metaiodobenzylguanidine treatment for metastatic carcinoid. Results in 98 patients. Cancer 101(9):1987–1993PubMedCrossRef

43.

Salem R, Thurston KG (2006) 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 17(10):1571–1593PubMedCrossRef

44.

Samlowski WE, Eyre HJ, Sause WT (1986) Evaluation of the response of unresectable carcinoid tumors to radiotherapy. Int J Radiat Oncol Biol Physiol 12(3):301–305CrossRef

45.

Sarmiento JM, Que FG (2003) Hepatic surgery for metastases from neuroendocrine tumors. Surg Oncol Clin N Am 12(1):231–242PubMedCrossRef

46.

Schupak KD, Wallner KE (1991) The role of radiation therapy in the treatment of locally unresectable or metastatic carcinoid tumors. Int J Radiat Oncol Biol Physiol 20(3):489–495CrossRef

47.

Soreide O, Berstad T, Bakka A et al (1992) Surgical treatment as a principle in patients with advanced abdominal carcinoid tumors. Surgery 111(1):48–54PubMed

48.

Therasse E, Breittmayer F, Roche A et al (1993) Transcatheter chemoembolization of progressive carcinoid liver metastasis. Radiology 189(2):541–547PubMed

49.

Veenendaal LM, Borel Rinkes IH, Lips CJ, van Hillegersberg R (2006) Liver metastases of neuroendocrine tumours: early reduction of tumour load to improve life expectancy. World J Surg Oncol 4:35PubMedCrossRef

50.

Yao KA, Talamonti MS, Nemcek A et al (2001) Indications and results of liver resection and hepatic chemoembolization for metastatic gastrointestinal neuroendocrine tumors. Surgery 130(4):677–682; discussion 682–675

Title: Radioembolization of Symptomatic, Unresectable Neuroendocrine Hepatic Metastases Using Yttrium-90 Microspheres
Authors: Philipp M. Paprottka
Ralf-T. Hoffmann
Alexander Haug
Wieland H. Sommer
Franziska Raeßler
Christoph G. Trumm
Gerwin P. Schmidt
Nima Ashoori
Maximilian F. Reiser
Tobias F. Jakobs
Publication date: 01-04-2012
Publisher: Springer-Verlag
Published in: CardioVascular and Interventional Radiology / Issue 2/2012
Print ISSN: 0174-1551
Electronic ISSN: 1432-086X
DOI: https://doi.org/10.1007/s00270-011-0248-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Radioembolization of Symptomatic, Unresectable Neuroendocrine Hepatic Metastases Using Yttrium-90 Microspheres

Abstract

Purpose

Materials and Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Materials and Methods

Results

Conclusion

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