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Alternative Tumor-Targeting Strategies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
This radioactive microsphere technology was further developed by a number of pharmaceutical companies such as Biocompatibles UK Ltd which produced a product known as TheraSphereTM (now owned by Boston Scientific), and these treatments became known as Trans-Arterial Radio-Embolization (TARE), or Selective Internal Radiation Therapy (SIRT). In 2015, Oxford University Hospitals NHS Trust in the UK started recruiting patients as part of the global EPOCH clinical trial for bowel cancer that has spread to the liver and become resistant to chemotherapy. The EPOCH trial was designed to evaluate the TheraSphereTM technology which is based on glass microspheres 20–30 µM in diameter that contain the beta-emitting radioactive isotope Yttrium-90. In one part of the trial involving 43 treated patients, 20 (47%) had an objective tumor response based on reduction in tumor size alone, whereas 34 (79%) had a response when tumor reduction and/or necrosis were used as response measures.
Brachytherapy Applications and Radiopharmaceuticals
Published in Eric Ford, Primer on Radiation Oncology Physics, 2020
Isotopes used for radionuclide therapy have several key features: short half-life (5–15 hours), short-range particles to deliver dose (typically β or α particles), and photons for imaging. Table 2.1 shows properties of some of the relevant isotopes.131I. Approved by the FDA in the United States in 1974, it is used as a targeted treatment for thyroid cancer and hyperthyroidism because iodine accumulates naturally in the thyroid gland. Activities of 75 to 200 mCi are used depending on the disease.90Y. Used for liver metastases and hepatocellular carcinoma, 90Y is attached to small glass beads (20–30 mm) and injected intraarterially. Targeting is achieved because the tumor blood supply is preferentially from the artery vs. normal liver from the vein. Two formulations are Therasphere®, approved for use in 1999, and SIR-sphere, approved in 2002.223Ra-Chloride. This is used to treat castrate-resistant prostate cancers. Bony metastases are targeted due to the chemical similarity of chloride to calcium. This has some advantages over 90Sr-chloride which was approved for used in 1993.177Lu-dotatate. This compound is a somastatin analog which targets neuroendocrine tumors which overexpress the somastatin receptor.
Medical management of neuroendocrine gastroenteropancreatic tumors
Published in Demetrius Pertsemlidis, William B. Inabnet III, Michel Gagner, Endocrine Surgery, 2017
Liver-directed intra-arterial therapies available in the treatment of unresectable liver metastases include transarterial embolization (TAE), transarterial chemoembolization (TACE), and selective internal radiotherapy (SIRT) with yttrium 90 microspheres. For TAE or TACE, symptomatic responses have been reported in 53%–100% of patients (up to 55 months) and tumor reduction in about 35%–74%, with a progression-free survival (PFS) of about 18–20 months and 5-year survival of 40%–80% [7–10]. Yttrium 90 radioembolization has been shown to be an effective treatment for hepatic metastases and is well tolerated [11–13]. It involves injection of embolic resin spheres (SIR-spheres, Sirtex Medical Ltd.) or glass spheres (TheraSphere, BTG Inc.). Microspheres loaded with beta-emitting radioisotope yttrium 90 are injected into the tumor hepatic arterial supply. In a recent meta-analysis of 12 relevant studies, radiographic response rates according to Response Evaluation Criteria in Solid Tumors (RECIST) range from 12% to 80%. Disease-controlled rates, defined as complete response or partial response plus stable disease, range from 62% to 100%. An administered radioactivity median of 1.7 GBq (range 1.2–3.4 GBq) did not correlate with either the response or control rate. The median overall survival rate ranges from 14 up to 70 months, with a median of 28.5 months. The response rate correlated with the median survival (p = 0.008) [14]. It has been suggested that many factors, including prior surgery, size of target lesions, performance status, baseline chemistry value, Ki-67 index, presence of extrahepatic disease, and inability to deliver a specified dose, influence patient outcomes for treatment of hepatic metastases with yttrium 90 radioembolization [14].
Yttrium-90 for colorectal liver metastasis - the promising role of radiation segmentectomy as an alternative local cure
Published in International Journal of Hyperthermia, 2022
Pouya Entezari, Ahmed Gabr, Riad Salem, Robert J. Lewandowski
There are two Y90 radioembolization devices that have been studied for patients with CRLM: resin (SIR-Spheres®, Sirtex Medical Ltd., North Sydney, Australia) and glass (TheraSphere®, Boston Scientific, Natick, Massachusetts). Per the U.S Food and Drug Administration (FDA), SIR-Spheres is indicated for the treatment of unresectable metastatic liver tumors from primary CRC with adjuvant intra-hepatic artery chemotherapy of floxuridine. Meanwhile, TheraSphere is approved by FDA for local tumor control of solitary tumors (1-8 cm in diameter), in patients with unresectable HCC, Child-Pugh Score A cirrhosis, well-compensated liver function, no macrovascular invasion, and good performance status. To this date, a direct prospective comparison of resin and glass microspheres has not been conducted in metastatic CRC. However, several studies employing these devices have yielded comparable survival outcomes [20,21].
Association Between Curative Treatment after Transarterial Radioembolization and Better Survival Outcomes in Patients with Hepatocellular Carcinoma
Published in Cancer Investigation, 2021
Yuna Kim, Han Ah Lee, Jae Seung Lee, Mi Young Jeon, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Soon Ho Um, Yeon Seok Seo, Seung Up Kim
A pre-delivery angiographic mapping procedure, i.e., angiography with technetium-99 macro-aggregated albumin scanning, was performed to evaluate the hepatic artery, enteric collaterals within the anticipated arterial treatment zone, and hepatopulmonary shunt. TARE was performed after 2–3 weeks of administering a calculated dose of 90Y resin microsphere (SIR-Spheres®; Sirtex Medical, Sydney, Australia) or glass particles (TheraSphere®; Biocompatibles UK Ltd, Surrey, UK). The administered dose was determined on the basis of the planning angiogram and was prepared in the nuclear medicine department, according to the preparation guide provided by the manufacturer. The entire process of TARE was performed in accordance with previous guidelines (18,19).
A systematic literature review and network meta-analysis of first-line treatments for unresectable hepatocellular carcinoma based on data from randomized controlled trials
Published in Expert Review of Anticancer Therapy, 2021
Richard F. Pollock, Victoria K. Brennan, Suki Shergill, Fabien Colaone
In 2019, the National Institute for Health and Care Excellence (NICE) commenced a multiple technology appraisal (MTA) of SIRT in the treatment of patients with unresectable early-, intermediate-, or advanced-stage HCC. The MTA covers three SIRT technologies: Yttrium-90 (Y-90) resin microspheres (SIR-Spheres; Sirtex Medical), Y-90 glass microspheres (TheraSphere; Boston Scientific), and Holmium-166 Poly(L-lactic acid) microspheres (QuiremSpheres; Terumo Europe NV). There are fundamental differences in the radioisotopes and microsphere substrates employed in the three SIRT technologies that manifest as different half-lives, embolic material density, radioactivity per microsphere, and a number of microspheres infused. QuiremSpheres uses a different radioisotope, whose effectiveness and safety in the treatment of HCC have not been demonstrated. Despite SIR-Spheres and TheraSphere using the same radioactive isotope (Y-90), higher amounts of injected radioactivity and radiation doses are recommended to achieve tumor response with TheraSphere compared to SIR-Spheres, suggesting different toxicity profiles, as higher injected radioactivity and radiation doses to the non-tumoral liver cells are associated with increased risks of liver complications [12–14]. Equal efficacy and safety can therefore not be assumed between the different SIRT technologies.