Selective internal radiation therapy

File:Radioembolisation.tif

Interventional radiologists performing radioembolisation

Other names| transarterial radioembolization (TARE)
Specialty| oncology

[edit on Wikidata]

Selective internal radiation therapy (SIRT), also known as transarterial radioembolization (TARE), radioembolization or intra-arterial microbrachytherapy is a form of radiation therapy used in interventional radiology to treat cancer. It is generally for selected patients with surgically unresectable cancers, especially hepatocellular carcinoma or metastasis to the liver. The treatment involves injecting tiny microspheres of radioactive material into the arteries that supply the tumor, where the spheres lodge in the small vessels of the tumor. Because this treatment combines radiotherapy with embolization, it is also called radioembolization. The chemotherapeutic analogue (combining chemotherapy with embolization) is called chemoembolization, of which transcatheter arterial chemoembolization (TACE) is the usual form.

## Contents

* 1 Principles
* 2 Therapeutic applications
* 3 Radionuclides and microspheres
* 4 Regulatory approval
* 4.1 United States
* 4.2 Europe
* 5 Procedure
* 6 Adverse effects
* 7 History
* 8 See also
* 9 References
* 10 External links

## Principles

Radiation therapy is used to kill cancer cells; however, normal cells are also damaged in the process. Currently, therapeutic doses of radiation can be targeted to tumors with great accuracy using linear accelerators in radiation oncology; however, when irradiating using external beam radiotherapy, the beam will always need to travel through healthy tissue, and the normal liver tissue is very sensitive to radiation.[1] The radiation sensitivity of the liver parenchyma limits the radiation dose that can be delivered via external beam radiotherapy. SIRT, on the other hand, involves the direct insertion of radioactive microspheres to a region, resulting in a local and targeted deposition of radioactive dose. It is therefore well-suited for treatment of liver tumors. Due to the local deposition, SIRT is regarded as a type of locoregional therapy (LRT).[citation needed]

The liver has a dual blood supply system; it receives blood from both the hepatic artery and the portal vein. The healthy liver tissue is mainly perfused by the portal vein, while most liver malignancies derive their blood supply from the hepatic artery. Therefore, locoregional therapies such as transarterial chemoembolization or radioembolization, can selectively be administered in the arteries that are supplying the tumors and will preferentially lead to deposition of the particles in the tumor, while sparing the healthy liver tissue from harmful side effects.[2]

In addition, malignancies (including primary and many metastatic liver cancers) are often hypervascular; tumor blood supplies are increased compared to those of normal tissue, further leading to preferential deposition of particles in the tumors.[citation needed]

SIRT can be performed using several techniques, including whole liver treatment, lobar or segmental approaches. Whole liver SIRT targets the entire liver in one treatment and can be used when the disease is spread throughout the liver. Radiation lobectomy targets one of the two liver lobes and can be a good treatment option when only a single lobe is involved or when treating the whole liver in two separate treatments, one lobe at the time. The segmental approach, also called radiation segmentectomy, is a technique where a high dose of radiation is delivered in one or two Couinaud liver segments only. The high dose results in eradication of the tumor while damage to healthy liver tissue is contained to the targeted segments only. This approach results in effective necrosis of the targeted segments. Segmentectomy is only feasible when the tumor(s) are contained in one or two segments. Which technique is applied is determined by catheter placement. The more distally the catheter is placed, the more localized the technique.[3]

## Therapeutic applications

Candidates for radioembolization include patients with:

1) Unresectable liver cancer of primary or secondary origin, such as hepatocellular carcinoma[4] and liver-metastases from a different origin (e.g. colorectal cancer,[5] breast cancer,[6] neuroendocrine cancer,[7] cholangiocarcinoma[8] or soft tissue sarcomas[9])
2) No response or intolerance to regional or systemic chemotherapy
3) No eligibility for potentially curative options such as radiofrequency ablation.[10]

SIRT is currently considered as a salvage therapy. It has been shown to be safe and effective in patients for whom surgery is not possible, and chemotherapy was not effective.[4][5][11][7][8] Subsequently, several large phase III trials have been started to evaluate the efficacy of SIRT when used earlier in the treatment scheme or in combination treatments with systemic therapy.

SIRT, when added to first line therapy for patients with metastases of colorectal cancer, was evaluated in the SIRFLOX,[12] FOXFIRE[13] and FOXFIRE Global[14] studies. For primary liver cancer (HCC), two large trials comparing SIRT with standard of care chemotherapy, Sorafenib, have been completed, namely the SARAH[15] and SIRveNIB[16] trials.

Results of these studies, published in 2017 and 2018, reported no superiority of SIRT over chemotherapy in terms of overall survival (SARAH,[17] SIRveNIB,[18] FOXFIRE[19]). In the SIRFLOX study, better progression-free survival was also not observed.[20] These trials did not give direct evidence supporting SIRT as a first-line treatment regime for liver cancer. However, these studies did show that SIRT is generally better tolerated than systemic therapy, with less severe adverse events. Simultaneously, for HCC, data derived from a large retrospective analysis showed promising results for SIRT as an earlier stage treatment, particularly with high dose radiation segmentectomy and lobectomy.[21]

More studies and cohort analyses are underway to evaluate subgroups of patients who benefit from SIRT as a first-line or later treatment, or to evaluate the effect of SIRT in combination with chemotherapy (EPOCH,[22] SIR-STEP,[23] SORAMIC,[24] STOP HCC[25]).

For HCC patients currently ineligible for liver transplant, SIRT can sometimes be used to decreases tumor size allowing patients to be candidates for curative treatment. This is sometimes called bridging therapy.[26]

When comparing SIRT with transarterial chemoembolization (TACE), several studies have shown favorable results for SIRT, such as longer time to progression,[27] higher complete response rates and longer progression-free survival.[28]

## Radionuclides and microspheres

There are currently three types of commercially available microsphere for SIRT. Two of these use the radionuclide yttrium-90 (90Y) and are made of either glass (TheraSphere) or resin (SIR-Spheres). The third type uses holmium-166 (166Ho) and is made of poly(l-lactic acid), PLLA, (QuiremSpheres). The therapeutic effect of all three types is based on local deposition of radiation dose by high-energy beta particles. All three types of microsphere are permanent implants and stay in the tissue even after radioactivity has decayed.

90Y, a pure beta emitter, has half-life 2.6 days, or 64.1 hours. 166Ho emits both beta and gamma rays emitter, with half-life 26.8 hours. Both 90Y and 166Ho have mean tissue penetration of a few millimeters. 90Y can be imaged using bremsstrahlung SPECT and positron emission tomography (PET). Bremsstrahlung SPECT uses of the approximately 23000 Bremsstrahlung photons per megabecquerel that are produced by interaction of beta particles with tissue. The positrons needed for PET imaging come from a small branch of the decay chain (branching ratio 32×10−6) that gives positrons.[29] 90Y's low bremsstrahlung photon and positron yield make it difficult to perform quantitative imaging.[30]

166Ho's additional gamma emission (81 KeV, 6.7%) makes 166Ho microspheres quantifiable using a gamma camera. Holmium is also paramagnetic, enabling visibility and quantifiability in MRI even after the radioactivity has decayed.[31]

Trade name  | SIR-Spheres  | TheraSphere  | QuiremSpheres

|
|
|

Manufacturer  | Sirtex Medical | Boston Scientific  | Quirem Medical (Terumo)
Mean diameter (μm)  | 32[32] | 25[32] | 30[33]
Specific gravity (g/dL) (compared to blood)  | 1.6 (150%)[34] | 3.6 (300%)[34] | 1.4 (130%)[35]
Activity per particle (Bq)  | 40-70[32] | 1250-2500[36] | 330-450[33]
Microspheres per 3 GBq vial (millions)  | 40-80[34] | 1.2[34] | 40-80[37]
Material  | Resin with bound yttrium  | Glass with yttrium in matrix  | PLLA with holmium
Radionuclide (half-life)  | 90Y (64.1 hours)  | 90Y (64.1 hours)  | 166Ho (26.8 hours)
Beta-radiation (MeV) (Emax)  | 2.28[38] | 2.28  | 1.77 (48.7%)[39]

1.85 (50.0%)

Gamma-radiation (keV)  | \-  | \-  | 81 (6.7%)

## Regulatory approval

### United States

Theraspheres (glass 90Y microspheres) are FDA approved under a humanitarian device exemption for hepatocellular carcinoma (HCC). SIR-spheres (resin 90Y microspheres) are FDA approved under premarket approval for colorectal metastases in combination with chemotherapy.[40]

### Europe

SIR-Spheres were CE-marked as a medical device in 2002, for treating advanced inoperable liver tumors, and Theraspheres in 2014, for treating hepatic neoplasia.[37] QuiremSpheres (PLLA 166Ho microspheres) received their CE mark in April 2015 for treating unresectable liver tumors and are currently only available for the European market.[37][41]

## Procedure

90Y microsphere treatment requires patient-individualized planning with cross-sectional imaging and arteriograms.[42] Contrast computed tomography and/or contrast-enhanced magnetic resonance imaging of the liver is required to assess tumor and normal liver volumes, portal vein status, and extrahepatic tumor burden. Liver and kidney function tests should be performed; patients with irreversibly elevated serum bilirubin, AST and ALT are excluded, as these are markers of poor liver function.[43] Use of iodinated contrast should be avoided or minimized in patients with chronic kidney disease. Tumor marker levels are also evaluated. Hepatic artery technetium (99mTc) macro aggregated albumin (MAA) scan is performed to evaluate hepatopulmonary shunting (resulting from hepatopulmonary syndrome). Therapeutic radioactive particles travelling through such a shunt can result in a high absorbed radiation dose to the lungs, possibly resulting in radiation pneumonitis. Lung dose >30 gray means increased risk of such pneumonitis.[44]

Initial angiographic evaluation can include an abdominal aortogram, Superior mesenteric and Celiac arteriograms, and selective right and left liver arteriograms. These tests can show gastrointestinal vascular anatomy and flow characteristics. Extrahepatic vessels found on angiographic evaluation can be embolized, to prevent nontarget deposition of microspheres, that can lead to gastrointestinal ulcers. Or the catheter tip can be moved more distally, past the extrahepatic vessels.[45] Once the branch of the hepatic artery supplying the tumor is identified and the tip of the catheter is selectively placed within the artery, the 90Y or 166Ho microspheres are infused. If preferred, particle infusion can be alternated with contrast infusion, to check for stasis or backflow. Radiation dose absorbed, depends on microsphere distribution within the tumor vascularization. Equal distribution is necessary to ensure tumor cells are not spared due to ~2.5mm mean tissue penetration, with maximum penetration up to 11mm for 90Y[46] or 8.7mm for 166Ho.[47]

After treatment, for 90Y microspheres, bremsstrahlung SPECT or PET scanning may be done within 24 hours after radioembolization to evaluate the distribution. For 166Ho microspheres, quantitative SPECT or MRI can be done. Weeks after treatment, computed tomography or MRI can be done to evaluate anatomic changes. 166Ho microspheres are still visible on MRI after radioactivity has decayed, because holmium is paramagnetic. FDG positron emission tomography may also be done to evaluate changes in metabolic activity.

## Adverse effects

Complications include postradioembolization syndrome (PRS), hepatic complications, biliary complications, portal hypertension and lymphopenia. Complications due to extrahepatic deposition include radiation pneumonitis, gastrointestinal ulcers and vascular injury.[48]

Postradioembolization syndrome (PRS) includes fatigue, nausea, vomiting, abdominal discomfort or pain, and cachexia, occurring in 20-70% of patients. Steroids and antiemetic agents may decrease the incidence of PRS.[49]

Liver complications include cirrhosis leading to portal hypertension, radioembolization-induced liver disease (REILD), transient elevations in liver enzymes, and fulminant liver failure.[49] REILD is characterized by jaundice, ascites, hyperbilirubinemia and hypoalbuminemia developing at least 2 weeks-4 months after SIRT, absent tumor progression or biliary obstruction. It can range from minor to fatal and is related to (over)exposure of healthy liver tissue to radiation.[49][50]

Biliary complications include cholecystitis and biliary strictures.

## History

Investigation of yttrium-90 and other radioisotopes for cancer treatment began in the 1960s. Many key concepts, such as preferential blood supply and tumor vascularity, were discovered during this time. Reports of initial use of resin particles of 90Y in humans were published in the late 1970s. In the 1980s, the safety and feasibility of resin and glass yttrium-90 microsphere therapy for liver cancer were validated in a canine model. Clinical trials of yttrium-90 applied to the liver continued throughout the late 1980s to the 1990s, establishing the safety of the therapy. More recently, larger trials and RCTs have shown safety and efficacy of 90Y therapy for the treatment of both primary and metastatic liver malignancies.[40][51]

Development of holmium-166 microspheres started in the 1990s. The intention was to develop a microsphere with therapeutic radiation dose similar to 90Y, but with better imaging properties, so that distribution of microspheres in the liver could be assessed more precisely. In the 2000s, development progressed to animal studies. 166Ho microspheres for SIRT were first used in humans in 2009, which was first published in 2012.[52] Since then, several trials have been performed showing safety and efficacy of 166Ho SIRT,[53] and more studies are ongoing.[54]

## See also

* Targeted alpha-particle therapy
* Transcatheter arterial chemoembolization

## References

1. ↑ Cromheecke, M.; Konings, A. W.; Szabo, B. G.; Hoekstra, H. J. (November 2000). "Liver tissue tolerance for irradiation: experimental and clinical investigations". Hepato-Gastroenterology 47 (36): 1732–1740. ISSN 0172-6390. PMID 11149044.
2. ↑ Gates, Vanessa L; Atassi, Bassel; Lewandowski, Robert J; Ryu, Robert K; Sato, Kent T; Nemcek, Albert A; Omary, Reed; Salem, Riad (2007-02-05). "Radioembolization with Yttrium-90 microspheres: review of an emerging treatment for liver tumors" (in EN). Future Oncology 3 (1): 73–81. doi:10.2217/14796694.3.1.73. PMID 17280504.
3. ↑ Riaz, Ahsun; Gates, Vanessa L.; Atassi, Bassel; Lewandowski, Robert J.; Mulcahy, Mary F.; Ryu, Robert K.; Sato, Kent T.; Baker, Talia et al. (2011). "Radiation Segmentectomy: A Novel Approach to Increase Safety and Efficacy of Radioembolization". International Journal of Radiation Oncology, Biology, Physics 79 (1): 163–171. doi:10.1016/j.ijrobp.2009.10.062. PMID 20421150.
4. ↑ 4.0 4.1 Salem, Riad; Lewandowski, Robert J.; Mulcahy, Mary F.; Riaz, Ahsun; Ryu, Robert K.; Ibrahim, Saad; Atassi, Bassel; Baker, Talia et al. (January 2010). "Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes". Gastroenterology 138 (1): 52–64. doi:10.1053/j.gastro.2009.09.006. ISSN 1528-0012. PMID 19766639.
5. ↑ 5.0 5.1 Van Cutsem, E.; Cervantes, A.; Adam, R.; Sobrero, A.; Krieken, Van; H, J.; Aderka, D.; Aranda Aguilar, E. et al. (2016-08-01). "ESMO consensus guidelines for the management of patients with metastatic colorectal cancer" (in en). Annals of Oncology 27 (8): 1386–1422. doi:10.1093/annonc/mdw235. ISSN 0923-7534. PMID 27380959.
6. ↑ Smits, Maarten L. J.; Prince, Jip F.; Rosenbaum, Charlotte E. N. M.; van den Hoven, Andor F.; Nijsen, J. Frank W.; Zonnenberg, Bernard A.; Seinstra, Beatrijs A.; Lam, Marnix G. E. H. et al. (2013-06-05). "Intra-arterial radioembolization of breast cancer liver metastases: a structured review". European Journal of Pharmacology 709 (1–3): 37–42. doi:10.1016/j.ejphar.2012.11.067. ISSN 1879-0712. PMID 23545356.
7. ↑ 7.0 7.1 Elf, Anna-Karin; Andersson, Mats; Henrikson, Olof; Jalnefjord, Oscar; Ljungberg, Maria; Svensson, Johanna; Wängberg, Bo; Johanson, Viktor (2018-02-01). "Radioembolization Versus Bland Embolization for Hepatic Metastases from Small Intestinal Neuroendocrine Tumors: Short-Term Results of a Randomized Clinical Trial" (in en). World Journal of Surgery 42 (2): 506–513. doi:10.1007/s00268-017-4324-9. ISSN 0364-2313. PMID 29167951.
8. ↑ 8.0 8.1 Benson, Al B.; Geschwind, Jean-Francois; Mulcahy, Mary F.; Rilling, William; Siskin, Gary; Wiseman, Greg; Cunningham, James; Houghton, Bonny et al. (2013). "Radioembolisation for liver metastases: Results from a prospective 151 patient multi-institutional phase II study". European Journal of Cancer 49 (15): 3122–3130. doi:10.1016/j.ejca.2013.05.012. PMID 23777743.
9. ↑ Testa, Stefano; Bui, Nam Q.; Wang, David S.; Louie, John D.; Sze, Daniel Y.; Ganjoo, Kristen N. (10 January 2022). "Efficacy and Safety of Trans-Arterial Yttrium-90 Radioembolization in Patients with Unresectable Liver-Dominant Metastatic or Primary Hepatic Soft Tissue Sarcomas". Cancers 14 (2): 324. doi:10.3390/cancers14020324. PMID 35053486.
10. ↑ Bennink, Roelof J.; Cieslak, Kasia P.; Delden, Van; M, Otto; Lienden, Van; P, Krijn; Klümpen, Heinz-Josef; Jansen, Peter L. et al. (2014). "Monitoring of Total and Regional Liver Function after SIRT" (in English). Frontiers in Oncology 4: 152. doi:10.3389/fonc.2014.00152. ISSN 2234-943X. PMID 24982851.
11. ↑ Fendler, Wolfgang P.; Lechner, Hanna; Todica, Andrei; Paprottka, Karolin J.; Paprottka, Philipp M.; Jakobs, Tobias F.; Michl, Marlies; Bartenstein, Peter et al. (2016-04-01). "Safety, Efficacy, and Prognostic Factors After Radioembolization of Hepatic Metastases from Breast Cancer: A Large Single-Center Experience in 81 Patients" (in en). Journal of Nuclear Medicine 57 (4): 517–523. doi:10.2967/jnumed.115.165050. ISSN 0161-5505. PMID 26742710.
12. ↑ "FOLFOX Plus SIR-SPHERES MICROSPHERES Versus FOLFOX Alone in Patients With Liver Mets From Primary Colorectal Cancer - Full Text View - ClinicalTrials.gov" (in en). https://clinicaltrials.gov/ct2/show/NCT00724503.
13. ↑ Sharma, Ricky (in en). ISRCTN - ISRCTN83867919: FOXFIRE: an open-label randomised phase III trial of 5-Fluorouracil, OXaliplatin and Folinic acid +/- Interventional Radio-Embolisation as first line treatment for patients with unresectable liver-only or liver-predominant metastatic colorectal cancer. doi:10.1186/ISRCTN83867919. http://www.isrctn.com/ISRCTN83867919. Retrieved 2018-03-29.
14. ↑ "FOLFOX6m Plus SIR-Spheres Microspheres vs FOLFOX6m Alone in Patients With Liver Mets From Primary Colorectal Cancer - Full Text View - ClinicalTrials.gov" (in en). https://clinicaltrials.gov/ct2/show/NCT01721954.
15. ↑ "SorAfenib Versus RADIOEMBOLIZATION in Advanced Hepatocellular Carcinoma - Full Text View - ClinicalTrials.gov" (in en). https://clinicaltrials.gov/ct2/show/NCT01482442?term=NCT01482442.
16. ↑ "Study to Compare Selective Internal Radiation Therapy (SIRT) Versus Sorafenib in Locally Advanced Hepatocellular Carcinoma (HCC) - Full Text View - ClinicalTrials.gov" (in en). https://clinicaltrials.gov/ct2/show/NCT01135056.
17. ↑ Vilgrain, Valérie; Pereira, Helena; Assenat, Eric; Guiu, Boris; Ilonca, Alina Diana; Pageaux, Georges-Philippe; Sibert, Annie; Bouattour, Mohamed et al. (2017). "Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial". The Lancet Oncology 18 (12): 1624–1636. doi:10.1016/s1470-2045(17)30683-6. PMID 29107679.
18. ↑ Chow, Pierce K.H.; Gandhi, Mihir; Tan, Say-Beng; Khin, Maung Win; Khasbazar, Ariunaa; Ong, Janus; Choo, Su Pin; Cheow, Peng Chung et al. (2018-03-02). "SIRveNIB: Selective Internal Radiation Therapy Versus Sorafenib in Asia-Pacific Patients With Hepatocellular Carcinoma". Journal of Clinical Oncology 36 (19): 1913–1921. doi:10.1200/jco.2017.76.0892. ISSN 0732-183X. PMID 29498924.
19. ↑ Wasan, Harpreet S.; Gibbs, Peter; Sharma, Navesh K.; Taieb, Julien; Heinemann, Volker; Ricke, Jens; Peeters, Marc; Findlay, Michael et al. (September 2017). "First-line selective internal radiotherapy plus chemotherapy versus chemotherapy alone in patients with liver metastases from colorectal cancer (FOXFIRE, SIRFLOX, and FOXFIRE-Global): a combined analysis of three multicentre, randomised, phase 3 trials". The Lancet. Oncology 18 (9): 1159–1171. doi:10.1016/S1470-2045(17)30457-6. PMID 28781171.
20. ↑ van Hazel, Guy A.; Heinemann, Volker; Sharma, Navesh K.; Findlay, Michael P. N.; Ricke, Jens; Peeters, Marc; Perez, David; Robinson, Bridget A. et al. (2016-05-20). "SIRFLOX: Randomized Phase III Trial Comparing First-Line mFOLFOX6 (Plus or Minus Bevacizumab) Versus mFOLFOX6 (Plus or Minus Bevacizumab) Plus Selective Internal Radiation Therapy in Patients With Metastatic Colorectal Cancer". Journal of Clinical Oncology 34 (15): 1723–1731. doi:10.1200/JCO.2015.66.1181. ISSN 1527-7755. PMID 26903575.
21. ↑ Salem, Riad; Gabr, Ahmed; Riaz, Ahsun; Mora, Ronald; Ali, Rehan; Abecassis, Michael; Hickey, Ryan; Kulik, Laura et al. (2017-12-01). "Institutional decision to adopt Y90 as primary treatment for hepatocellular carcinoma informed by a 1,000-patient 15-year experience". Hepatology 68 (4): 1429–1440. doi:10.1002/hep.29691. ISSN 1527-3350. PMID 29194711.
22. ↑ "Efficacy Evaluation of TheraSphere Following Failed First Line Chemotherapy in Metastatic Colorectal Cancer - Full Text View - ClinicalTrials.gov" (in en). https://clinicaltrials.gov/ct2/show/NCT01483027.
23. ↑ "Comparing HAI-90Y (SIR-spheres)+Chemotx LV5FU2 Versus Chemotx LV5FU2 Alone to Treat Colorectal Cancer - Full Text View - ClinicalTrials.gov" (in en). https://clinicaltrials.gov/ct2/show/NCT01895257.
24. ↑ "Sorafenib and Micro-therapy Guided by Primovist Enhanced MRI in Patients With Inoperable Liver Cancer - Full Text View - ClinicalTrials.gov" (in en). https://clinicaltrials.gov/ct2/show/NCT01126645.
25. ↑ "Efficacy Evaluation of TheraSphere in Patients With Inoperable Liver Cancer - Full Text View - ClinicalTrials.gov" (in en). https://clinicaltrials.gov/ct2/show/NCT01556490.
26. ↑ Levi Sandri, Giovanni Battista; Ettorre, Giuseppe Maria; Giannelli, Valerio; Colasanti, Marco; Sciuto, Rosa; Pizzi, Giuseppe; Cianni, Roberto; D'Offizi, Gianpiero et al. (2017-11-27). "Trans-arterial radio-embolization: a new chance for patients with hepatocellular cancer to access liver transplantation, a world review" (in en). Translational Gastroenterology and Hepatology 2 (11): 98. doi:10.21037/tgh.2017.11.11. PMID 29264436.
27. ↑ Salem, Riad; Gordon, Andrew C.; Mouli, Samdeep; Hickey, Ryan; Kallini, Joseph; Gabr, Ahmed; Mulcahy, Mary F.; Baker, Talia et al. (2016). "Y90 Radioembolization Significantly Prolongs Time to Progression Compared With Chemoembolization in Patients With Hepatocellular Carcinoma". Gastroenterology 151 (6): 1155–1163.e2. doi:10.1053/j.gastro.2016.08.029. PMID 27575820.
28. ↑ Padia, Siddharth A.; Johnson, Guy E.; Horton, Kathryn J.; Ingraham, Christopher R.; Kogut, Matthew J.; Kwan, Sharon; Vaidya, Sandeep; Monsky, Wayne L. et al. (2017). "Segmental Yttrium-90 Radioembolization versus Segmental Chemoembolization for Localized Hepatocellular Carcinoma: Results of a Single-Center, Retrospective, Propensity Score–Matched Study". Journal of Vascular and Interventional Radiology 28 (6): 777–785.e1. doi:10.1016/j.jvir.2017.02.018. PMID 28365172.
29. ↑ Elschot, Mattijs; Vermolen, Bart J.; Lam, Marnix G. E. H.; Keizer, Bart de; Bosch, Maurice A. A. J. van den; Jong, Hugo W. A. M. de (2013-02-06). "Quantitative Comparison of PET and Bremsstrahlung SPECT for Imaging the In Vivo Yttrium-90 Microsphere Distribution after Liver Radioembolization" (in en). PLOS ONE 8 (2): e55742. doi:10.1371/journal.pone.0055742. ISSN 1932-6203. PMID 23405207. Bibcode: 2013PLoSO...855742E.
30. ↑ Smits, Maarten L. J.; Elschot, Mattijs; Sze, Daniel Y.; Kao, Yung H.; Nijsen, Johannes F. W.; Iagaru, Andre H.; de Jong, Hugo W. A. M.; van den Bosch, Maurice A. A. J. et al. (April 2015). "Radioembolization dosimetry: the road ahead". CardioVascular and Interventional Radiology 38 (2): 261–269. doi:10.1007/s00270-014-1042-7. ISSN 1432-086X. PMID 25537310.
31. ↑ Smits, Maarten L. J.; Elschot, Mattijs; van den Bosch, Maurice A. A. J.; van de Maat, Gerrit H.; van het Schip, Alfred D.; Zonnenberg, Bernard A.; Seevinck, Peter R.; Verkooijen, Helena M. et al. (December 2013). "In vivo dosimetry based on SPECT and MR imaging of 166Ho-microspheres for treatment of liver malignancies". Journal of Nuclear Medicine 54 (12): 2093–2100. doi:10.2967/jnumed.113.119768. ISSN 1535-5667. PMID 24136931.
32. ↑ 32.0 32.1 32.2 Giammarile, Francesco; Bodei, Lisa; Chiesa, Carlo; Flux, Glenn; Forrer, Flavio; Kraeber-Bodere, Françoise; Brans, Boudewijn; Lambert, Bieke et al. (July 2011). "EANM procedure guideline for the treatment of liver cancer and liver metastases with intra-arterial radioactive compounds". European Journal of Nuclear Medicine and Molecular Imaging 38 (7): 1393–1406. doi:10.1007/s00259-011-1812-2. PMID 21494856. https://dipot.ulb.ac.be/dspace/bitstream/2013/340543/1/doi_324187.pdf.
33. ↑ 33.0 33.1 d’Abadie, Philippe; Hesse, Michel; Louppe, Amandine; Lhommel, Renaud; Walrand, Stephan; Jamar, Francois (29 June 2021). "Microspheres Used in Liver Radioembolization: From Conception to Clinical Effects". Molecules 26 (13): 3966. doi:10.3390/molecules26133966. PMID 34209590.
34. ↑ 34.0 34.1 34.2 34.3 Westcott, Mark A.; Coldwell, Douglas M.; Liu, David M.; Zikria, Joseph F. (October 2016). "The development, commercialization, and clinical context of yttrium-90 radiolabeled resin and glass microspheres". Advances in Radiation Oncology 1 (4): 351–364. doi:10.1016/j.adro.2016.08.003. PMID 28740906.
35. ↑ Bombardieri, Emilio; Seregni, Ettore; Evangelista, Laura; Chiesa, Carlo; Chiti, Arturo (2018) (in en). Clinical Applications of Nuclear Medicine Targeted Therapy. Cham: Springer. p. 113. doi:10.1007/978-3-319-63067-0. ISBN 9783319630663. https://books.google.com/books?id=uHpTDwAAQBAJ&pg=PA113.
36. ↑ Vente, M. A. D.; Wondergem, M.; van der Tweel, I.; van den Bosch, M. A. A. J.; Zonnenberg, B. A.; Lam, M. G. E. H.; van het Schip, A. D.; Nijsen, J. F. W. (April 2009). "Yttrium-90 microsphere radioembolization for the treatment of liver malignancies: a structured meta-analysis". European Radiology 19 (4): 951–959. doi:10.1007/s00330-008-1211-7. PMID 18989675.
37. ↑ 37.0 37.1 37.2 "Information about QuiremSpheres, SIR-Spheres and TheraSphere | Selective internal radiation therapies for treating hepatocellular carcinoma | Technology appraisal guidance [TA688"]. 31 March 2021. https://www.nice.org.uk/guidance/ta688/chapter/2-Information-about-QuiremSpheres-SIR-Spheres-and-TheraSphere.
38. ↑ Chu, S Y F; Ekström, L P; Firestone, R B (1999). "Yttrium-99". Lund University. http://nucleardata.nuclear.lu.se/toi/nuclide.asp?iZA=390099.
39. ↑ Chu, S Y F; Ekström, L P; Firestone, R B (1999). "Holmium-166". Lund University. http://nucleardata.nuclear.lu.se/toi/nuclide.asp?iZA=670166.
40. ↑ 40.0 40.1 Westcott, Mark A.; Coldwell, Douglas M.; Liu, David M.; Zikria, Joseph F. (2016). "The development, commercialization, and clinical context of yttrium-90 radiolabeled resin and glass microspheres". Advances in Radiation Oncology 1 (4): 351–364. doi:10.1016/j.adro.2016.08.003. PMID 28740906.
41. ↑ "QuiremSpheres". https://www.quirem.com/quiremspheres/.
42. ↑ Kennedy, A 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 Phys 68 (1): 13–23. doi:10.1016/j.ijrobp.2006.11.060. PMID 17448867.
43. ↑ Boas, F. Edward; Bodei, Lisa; Sofocleous, Constantinos T. (September 2017). "Radioembolization of Colorectal Liver Metastases: Indications, Technique, and Outcomes". Journal of Nuclear Medicine 58 (Suppl 2): 104S–111S. doi:10.2967/jnumed.116.187229. ISSN 1535-5667. PMID 28864605.
44. ↑ Cremonesi, Marta; Chiesa, Carlo; Strigari, Lidia; Ferrari, Mahila; Botta, Francesca; Guerriero, Francesco; De Cicco, Concetta; Bonomo, Guido et al. (2014). "Radioembolization of hepatic lesions from a radiobiology and dosimetric perspective". Frontiers in Oncology 4: 210. doi:10.3389/fonc.2014.00210. PMID 25191640.
45. ↑ Braat, Arthur J. A. T.; Smits, Maarten L. J.; Braat, Manon N. G. J. A.; van den Hoven, Andor F.; Prince, Jip F.; de Jong, Hugo W. A. M.; van den Bosch, Maurice A. A. J.; Lam, Marnix G. E. H. (July 2015). "90Y Hepatic Radioembolization: An Update on Current Practice and Recent Developments". Journal of Nuclear Medicine 56 (7): 1079–1087. doi:10.2967/jnumed.115.157446. ISSN 1535-5667. PMID 25952741.
46. ↑ Singh P, Anil G. Yttrium-90 radioembolization of liver tumors: what do the images tell us?. Cancer Imaging. 2014;13(4):645-57.
47. ↑ Prince, Jip F.; Smits, Maarten L. J.; Krijger, Gerard C.; Zonnenberg, Bernard A.; van den Bosch, Maurice A. A. J.; Nijsen, Johannes F. W.; Lam, Marnix G. E. H. (December 2014). "Radiation emission from patients treated with holmium-166 radioembolization". Journal of Vascular and Interventional Radiology 25 (12): 1956–1963.e1. doi:10.1016/j.jvir.2014.09.003. ISSN 1535-7732. PMID 25311966.
48. ↑ Riaz, A et al. (2009). "Complications Following Radioembolization with Yttrium-90 Microspheres: A Comprehensive Literature Review". Journal of Vascular and Interventional Radiology 20 (9): 1121–1130. doi:10.1016/j.jvir.2009.05.030. PMID 19640737.
49. ↑ 49.0 49.1 49.2 Riaz, Ahsun; Awais, Rafia; Salem, Riad (2014). "Side Effects of Yttrium-90 Radioembolization" (in English). Frontiers in Oncology 4: 198. doi:10.3389/fonc.2014.00198. ISSN 2234-943X. PMID 25120955.
50. ↑ Braat, Manon N.G.J.A.; Erpecum, Karel J. van; Zonnenberg, Bernard A.; Bosch, Maurice A.J. van den; Lam, Marnix G.E.H. (2017). "Radioembolization-induced liver disease". European Journal of Gastroenterology & Hepatology 29 (2): 144–152. doi:10.1097/meg.0000000000000772. PMID 27926660.
51. ↑ Atassi, B et al. (2007). "Radioembolization with Yttrium-90 microspheres: review of an emerging treatment for liver tumors". Future Oncology 3 (1): 73–81. doi:10.2217/14796694.3.1.73. PMID 17280504.
52. ↑ Smits, Maarten LJ; Nijsen, Johannes FW; Bosch, Maurice AAJ van den; Lam, Marnix GEH; Vente, Maarten AD; Mali, Willem PTM; Schip, Alfred D van het; Zonnenberg, Bernard A (2012). "Holmium-166 radioembolisation in patients with unresectable, chemorefractory liver metastases (HEPAR trial): a phase 1, dose-escalation study". The Lancet Oncology 13 (10): 1025–1034. doi:10.1016/s1470-2045(12)70334-0. PMID 22920685.
53. ↑ Prince, Jip F.; Bosch, Maurice A. A. J. van den; Nijsen, J. F. W.; Smits, Maarten L. J.; Hoven, Andor F. van den; Nikolakopoulos, Stavros; Wessels, Frank J.; Bruijnen, Rutger C. G. et al. (2017-09-15). "Efficacy of radioembolization with holmium-166 microspheres in salvage patients with liver metastases: a phase 2 study" (in en). Journal of Nuclear Medicine 59 (4): 582–588. doi:10.2967/jnumed.117.197194. ISSN 0161-5505. PMID 28916623. http://jnm.snmjournals.org/content/early/2017/09/15/jnumed.117.197194.
54. ↑ "Clinical | QuiremSpheres" (in en-US). http://www.quiremspheres.com/clinical.html.

## External links

* Phase III clinical trials of SIR-spheres
* Phase III clinical trials of Therasphere

* v
* t
* e

Radiation oncology

* (ICD-9-CM V3 92.2-92.3
* ICD-10-PCS D)

Specific
therapies

| Teletherapy1|

| by photon|

* Superficial X-rays
* Orthovoltage X-rays
* Megavoltage X-rays
* Radiosurgery / Stereotactic radiation therapy
* Cyberknife
* Gamma Knife
* Cobalt therapy

|

by electron|

* Electron therapy

by hadron|

* Particle therapy
* fast neutron
* neutron-capture
* proton

Brachytherapy2|

* Prostate
* 125I
* 103Pd
* Plaque radiotherapy (125I)
* Selective internal radiation therapy / SIR-Spheres / TheraSphere (90Y)

Unsealed source
radiotherapy3

* Iobenguane (131I)
* 90Y
* Lexidronam (153Sm)
* 89Sr
* Radioimmunotherapy
* ibritumomab tiuxetan

Other|

* Intraoperative radiation therapy
* electron
* TARGIT
* Tomotherapy

Conditions|

* Radiation burn
* Radiation proctitis
* Radiation-induced lung injury

Features and
equipment

* BEAMnrc
* Bolus
* Bragg peak
* D50
* Dose profile
* Dose verification system
* Dose-volume histogram
* Dosimetry
* Isocenter
* Mobetron
* Monitor unit
* Multileaf collimator
* Nanoimpellers
* Neutron generator
* Oxygen enhancement ratio
* Pencil
* Pencil-beam scanning
* Percentage depth dose curve
* Radiation oncologist
* Radiation Therapist
* Radiation treatment planning
* Radiopharmacology
* Tissue to Air Ratio (TAR)

* 1 Also known as external-beam radiotherapy.
* 2 Also known as sealed-source radiation therapy.
* 3 Also known as systemic radioisotope therapy.

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