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Liver
Liver Metastases follow-up positron emission tomography (PET). Eighty percent of patients
who were symptomatic received relief.
14
Another cohort was presented in
Colorectal Cancer Metastatic to the Liver 2006, where investigators reported 89% objective tumor response rate by
The mainstay of treatment for colorectal cancer is surgical resection, imaging and chromogranin A.
28
A large cohort of 113 patients with diverse
systemic chemotherapy, and radiation.
4,27
Patients with liver-dominant primaries (colon, neuroendocrine, pancreas, lung) was treated with
disease who have failed standard first- and second-line therapies may be radioembolization. Response by cross-sectional imaging and PET was 29
considered for treatment using
90
Y. The benefits of radioembolization with and 79%, respectively. Median survival from first treatment for all patients
90
Y in these patients has been reported in many studies.
5–10
A 43-patient was 10 months.
29
Pöpperl et al. recently reported on 23 patients with
cohort that underwent radioembolization with glass microspheres was unresectable hepatic malignancies treated with resin microspheres. Follow-
presented.
11
Median survival was 408 days. A study of 74 patients treated up data showed positive response in the majority of patients.
30
Thirty-four
with resin microspheres in combination with intrahepatic floxuridine was patients with extensive hepatic metastases were treated with resin
completed.
5
This was compared with patients receiving FUDR alone. The microspheres and 22 patients experienced 33 liver toxicities, the most
partial and complete response rate was significantly greater for patients frequent toxicity being increased aminotransferase, alkaline phosphatase,
receiving
90
Y when measured by tumor areas, tumor volumes, and and bilirubin levels. Two major adverse events were observed (gastric ulcers).
carcinoembryonic antigen (CEA). Investigators reported on a 50-patient Partial response was detected in approximately one-third of cases. It was
cohort with extensive colorectal liver metastases treated with concluded that whole-liver treatment with intra-arterial injection of
90
Y
radioembolization.
7
Median survival was 9.8 months. The same group microspheres in a single session is a safe and effective treatment option in
published on 38 patients with extensive colorectal liver metastases who patients with extensive hepatic metastases.
31,32
received resin microspheres.
6
Response to treatment as demonstrated by
decreasing tumor markers and serial three-monthly computed tomography Future Direction
(CT) scans were seen in over 90% of patients. Estimated survival at six, 12, There are several opportunities in the future development of
and 18 months was 70, 46, and 46%, respectively. A randomized study of radioembolization. Dose-planning microspheres permitting exact dose
21 patients (11 patients received resin microspheres + 5 fluorouracil (5FU)/ planning and tumor dosimetry would represent a significant advance.
leucovorin (LV); 10 patients received the 5FU/LV alone). Investigators Microspheres that can be imaged at the micron level would enhance the
observed that radioembolization along with a standard chemotherapeutic assessment of tumor response and distribution. Other tumors that may be
regimen significantly increased treatment-related response, time to disease targeted using this therapy include all those that are inherently
progression, and survival compared with chemotherapy alone.
12
A multi- hypervascular, including meningiomas, renal cell cancers, and
institutional cohort of 208 patients treated with radioembolization was neuroendocrine tumors. Combinatorial trials that involve dose fractionation
presented in 2006. Imaging response was 35%, while PET response was and escalation are required to further study the effect of this therapy with
91%. Survival was 10.5 and 4.5 months for responders and non- established chemotherapeutics. The role of this technology in downstaging
responders, respectively. It was concluded that radioembolization provided patients to liver transplantation, in HCC patients with portal vein
acceptable clinical toxicities and significant objective imaging responses, as thrombosis, and in those with metastatic disease to the liver refractory to
well as promising survival rates.
13
standard-of-care chemotherapy requires further investigation. Finally,
radiation segmentectomy represents an immense opportunity for
Liver Metastases radioembolization. Given the extremely high specific activity of the
There exists a non-colorectal patient population with liver-dominant disease microspheres, coupled with their mild to moderate embolic effect, it is
that is refractory to standard-of-care chemotherapies. In this clinical context, theoretically possible to safely irradiate tissue to levels approaching
radioembolization may play a significant role. An 84-patient cohort with 5,000Gy. This concept of ‘radiation segmentectomy’ may become a
neuroendocrine disease was published, demonstrating a 67% response on replacement for ablative technologies or surgical resection. ■
1. SIR-Spheres Yttrium-90 microspheres package insert, SIRTeX 2003;2:216–25. 23. Dancey JE, Shepherd FA, Paul K, et al., J Nucl Med, 2000;41(10):
Medical, Lane Cove, Australia, 2004. 12. Van Hazel G, Blackwell A, Anderson J, et al., J Surg Oncol, 1673–81.
2. Atassi B, Lewandowski RJ, Kulik L, et al., Society of Interventional 2004;88(2):78–85. 24. Carr BI, Liver Transpl, 2004;10(2 Suppl. 1):S107–10.
Radiology Annual Meeting, Toronto, Canada: Mar 30 – Apr 4, 13. Kennedy AS, Coldwell D, Nutting C, et al., Int J Radiat Oncol Biol 25. Geschwind JF, Salem R, Carr BI, et al., Gastroenterology,
2006. Phys, 2006;65(2):412–25. 2004;127(5 Suppl. 1):S194–205.
3. Kim DY, Kwon DS, Salem R, et al., J Gastrointest Surg, 2006;10(3): 14. Coldwell D, Nutting C, Kennedy AK, World Congress of 26. Sangro B, Bilbao JI, Boan J, et al., Int J Radiat Oncol Biol Phys, 2006.
413–16. Gastrointestinal Cancer. Barcelona, Spain: June 27–30, 2005. 27. Messersmith W, Laheru D, Hidalgo M, Expert Opin Investig Drugs,
4. Mulcahy MF, Benson AB 3rd, Opin Biol Ther, 2005;5(7):997–1005. 15. Kulik L, Atassi B, van Holsbeeck L, et al., J Surg Oncol, 2006; in press. 2003;12(3):423–34.
5. Gray B, Van Hazel G, Hope M, et al., Ann Oncol, 2001;12(12): 16. Kulik LM, Mulcahy MF, Hunter RD, et al., Liver Transpl, 2005;11(9): 28. Kennedy AS, McNeillie P, Overton C, et al., American
1711–20. 1127–31. Brachytherapy Society, Orlando, Florida: July 30 – Aug 3, 2006.
6. Stubbs RS, Cannan RJ, Mitchell AW, Hepatogastroenterology, 17. Lau WY, Ho SK, Yu SC, et al., Ann Surg, 2004;240(2):299–305. 29. Lewandowski RJ, Atassi BA, Wong CO, et al., Cardiovascular and
2001;48(38):333–7. 18. Lewandowski R, Salem R, Thurston K, et al., Radiological Society Interventional Society of Europe. Rome, Italy: Sept 9–13, 2006.
7. Stubbs RS, Cannan RJ, Mitchell AW, J Gastrointest Surg, of North America, Chicago: Nov 28 – Dec 3, 2004. 30. Popperl G, Helmberger T, Munzing W, et al., Cancer Biother
2001;5(3):294–302. 19. Rhee TK, Omary RA, Gates V, et al., J Vasc Interv Radiol, Radiopharm, 2005;20(2):200–8.
8. Rubin D, Nutting C, Jones B, Integr Cancer Ther, 2004;3(3):262–7. 2005;16(8):1085–91. 31. Jakobs TF, Hoffmann RT, Schmitz A, et al., Society of Interventional
9. Wong CY, Qing F, Savin M, et al., J Vasc Interv Radiol, 2005;16(8): 20. Salem R, Lewandowski RJ, Atassi B, et al., J Vasc Interv Radiol, Radiology Annual Meeting, Toronto, Canada: Mar 30 – Apr 4, 2006.
1101–6. 2005;6(12):1627–39. 32. Jakobs TF, Hoffmann RT, Schmitz A, et al., Society of Interventional
10. Murthy R, Xiong H, Nunez R, et al., J Vasc Interv Radiol, 21. TheraSphere Yttrium-90 microspheres package insert, MDS Radiology Annual Meeting. Toronto, Canada: Mar 30 – Apr 4, 2006.
2005;16(7):937–45. Nordion, Kanata, Canada, 2004.
11. Goin JE, Dancey JE, Hermann GA, et al., World J Nuc Med, 22. Okuda K, Ohtsuki T, Obata H, et al., Cancer, 1985;56(4):918–28.
52 US GASTROENTEROLOGY REVIEW 2007
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