Published online Jun 7, 2015. doi: 10.3748/wjg.v21.i21.6518
Peer-review started: December 1, 2014
First decision: January 22, 2015
Revised: March 13, 2015
Accepted: April 28, 2015
Article in press: April 28, 2015
Published online: June 7, 2015
Processing time: 192 Days and 5.7 Hours
In the last decade trans-arterial radioembolization has given promising results in the treatment of patients with intermediate or advanced stage hepatocellular carcinoma (HCC), both in terms of disease control and tolerability profile. This technique consists of the selective intra-arterial administration of microspheres loaded with a radioactive compound (usually Yttrium90), and exerts its therapeutic effect through the radiation carried by these microspheres. A careful and meticulous selection of patients is crucial before performing the radioembolization to correctly perform the procedure and reduce the incidence of complications. Radioembolization is a technically complex and expensive technique, which has only recently entered clinical practice and is supported by scant results from phase III clinical trials. Nevertheless, it may represent a valid alternative to transarterial chemoembolization (TACE) in the treatment of intermediate-stage HCC patients, as shown by a comparative retrospective assessment that reported a longer time to progression, but not of overall survival, and a more favorable safety profile for radioembolization. In addition, this treatment has reported a higher percentage of tumor shrinkage, if compared to TACE, for pre-transplant downsizing and it represents a promising therapeutic option in patients with large extent of disease and insufficient residual liver volume who are not immediately eligible for surgery. Radioembolization might also be a suitable companion to sorafenib in advanced HCC or it can be used as a potential alternative to this treatment in patients who are not responding or do not tolerate sorafenib.
Core tip: This review provides an overview of trans-arterial radioembolization, a new therapeutic option for patients with hepatocellular carcinoma. In particular, the practical aspects of the technique and available data on disease control will be presented, with reference to patients in either early or advanced stages of disease, treated with trans-arterial embolization alone or within combination regimens.
- Citation: Sacco R, Mismas V, Marceglia S, Romano A, Giacomelli L, Bertini M, Federici G, Metrangolo S, Parisi G, Tumino E, Bresci G, Corti A, Tredici M, Piccinno M, Giorgi L, Bartolozzi C, Bargellini I. Transarterial radioembolization for hepatocellular carcinoma: An update and perspectives. World J Gastroenterol 2015; 21(21): 6518-6525
- URL: https://www.wjgnet.com/1007-9327/full/v21/i21/6518.htm
- DOI: https://dx.doi.org/10.3748/wjg.v21.i21.6518
Hepatocellular carcinoma (HCC) ranks fifth among the most common cancers worldwide and represents the third most frequent cause of cancer-related mortality[1,2]. In the majority of cases, HCC is diagnosed in the intermediate-advanced stage [stage B and C according to the Barcelona Clinic Liver Cancer (BCLC) staging categories], when radical therapy is no longer possible. A number of curative and/or palliative therapies are available in this setting, but they are not always characterized by a favorable safety/efficacy ratio. Therefore, new therapeutic options are eagerly awaited.
Preliminary data on the use of trans-arterial radioembolization have demonstrated a good tolerability profile and promising results of this technique in terms of disease control. Although radioembolization has been studied more extensively in BCLC-B and BCLC-C HCC patients, its use has been evaluated also in the early stages (BCLC-A).
This review provides an overview of trans-arterial radioembolization. In particular, the practical aspects of the technique and available data on disease control will be presented, with reference to patients in either early or advanced stages of disease, treated with trans-arterial embolization alone or within combination regimens.
Trans-arterial radioembolization, also known simply as radioembolization or as selective internal radiation therapy, consists of the selective intra-arterial administration of microspheres loaded with a radioactive compound - usually Yttrium90 or Lipiodol labelled with iodine131 or rhenium188 - through a percutaneous access.
Yttrium90 is a pure β emitter characterized by short half-life (64.2 h) and limited tissue penetration (average 2.5 mm, maximum 11 mm). Two types of microspheres are available, namely TheraSphere®, made of glass, and Sir-Spheres®, made of resin. They differ in size, activity for individual bead, and number of microspheres injected (as shown in Table 1), but available data suggest the equivalence of the two methods[3]. Differing from other embolizing treatments such as trans-arterial chemoembolization (TACE), radioembolization does not exert a macroembolic effect: therefore, both the benefits and the toxic effects of the treatment are dependent upon the radiation carried by the microspheres and not by any ischemic effect.
| Sir-Spheres® | TheraSphere® | |
| Diameters (μm) | 32 ± 10 | 22 ± 10 |
| Specific weight (g/dL) | 1.6 | 3.6 |
| Activity per microsphere to date calibration (Bq) | 50 | 2500 |
| Number of microsphere (vial, million) | 40-80 | 1.2-8 |
| Material | Resin | Glass |
| Activity in the vial (GBq) | 3% ± 10% | 3, 5, 7, 10, 15 or 20 |
The different features of the two types of microspheres can explain the hypothetical different use for each patient and the difference in the mode of administration and in the activity calculation.
TheraSphere has a minimal embolic power (average number of glass microspheres injected: 4 million) with a higher activity for each sphere (2500 Bq vs 50 Bq for Sir-Spheres). These characteristics prevent vascular stasis and reflux during the administration, but in the case of a large lesion an inadequate coverage of the treated volume can occur, because the higher specific weight can limit the distribution of the microspheres.
On the other hand, Sir-Spheres, with a higher number of microspheres injected (average 40 million), have an important embolic power. Thanks to the number of microspheres injected it is possible to achieve an adequate and more homogeneous coverage of the lesion when compared with TheraSphere; however, the higher embolic power requires slow injections and accurate angiographic control during the administration.
The different coverage of the lesion is also reflected by the different median lethal dose: for Therasphere it oscillates between 205[4] and 257 Gy[5], instead for Sir-Spheres we can find a lower value, 120 Gy[6]. Of note, these values were calculated with the dosimetric approach, which differs from the empiric activity calculation method (described below).
The first studies on Yttrium90 for the treatment of oncological diseases date back to the 1960s[7,8]. However, radioembolization has entered clinical practice only in the last decade. Available evidence supports the potential effectiveness of Yttrium90 microspheres in the treatment of primary (HCC and cholangiocarcinoma) and metastatic liver cancer[9-12].
Radioembolization can be divided into consecutive stages: (1) patient pre-selection: a multidisciplinary assessment identifies patients possibly eligible for this therapy[13]; (2) patient selection: a diagnostic angiography is performed with the aim of evaluating vascular anatomy and to identify and embolize any extrahepatic branch which could disperse the microspheres to non-target organs[14]. Moreover, angiography allows the establishment of the most appropriate point of injection of the catheter. During this visit, macroaggregates of albumin (MAA) labeled with Tc99 are injected. They present a diffusion similar to that of radioembolization microspheres, and can help predict the distribution of the microspheres. The diffusion of these macroaggregates is studied by a single photon emission computed tomography (SPECT/CT), performed within 1 h from the injection[15]; After the selection phase, other contraindications might exclude patients from treatment. Among these, a hepato-pulmonary shunt > 20% of the injected dose[16] or vascular abnormalities not correctable by embolization; (3) dose calculation: the amount of Yttrium90 administered is determined specifically for each patient (as discussed below); and (4) injection of microspheres: microspheres are injected by a catheter no later than 4 wk from the selection of patients.
All the calculation activity methods used today are generally based on empiric data.
In order to perform the calculation of the activity (A) of TheraSphere to be injected, the following formula is generally used:
A = 120 (Gy) × M/[(1 - S) × 50]. Where M is the mass of the whole liver and S is the lung-liver shunt. 120 Gy is the dose (lethal dose) that we want to disburse to the lesion, assuming that there is a uniform distribution of the glass spheres in the target volume[17].
For Sir-Sphere, 3 methods are available for calculation activity[18]: (1) Empirical Method[18]. The amount of activity to be injected is chosen in relation to tumor over whole liver percentage (T): T < 25% → Gbq; 25% < T ≤ 50% → 2.5 GBq; T > 50% → 3 Gbq. With this method however, the dose to healthy liver is not considered and patients could be exposed to non-necessary radiation toxicity; (2) BSA-Method[18]. In the calculation of activity to be injected, the ratio between tumor lobe (where the lesion is localized) and whole liver volumes and the body surface area (BSA) of the patient are considered. This method accounts for the relation between the size of the patient and their liver and enables the treatment of different lesions in separate lobes, preserving healthy tissues; and (3) Partition model[16]. Following the Medical Internal Radiation Dose (MIRD) method, the partition model takes into account the different distribution of the microspheres in the lesions and in the healthy tissue. The evaluation of these distributions is based on the results of the SPECT/TC with 99mTc-MAA. A (GBq) = Dliver × [(T/N × Mtumor) + Mliver]49670 × (1 - S). Where Dliver is the dose to healthy liver (chosen by nuclear medicine physician in order to preserve it), Mliver is the whole organ mass, Mtumor is lesion mass, S is the lung-liver shunt and T/N is the ratio between activity over mass for tumor and liver: T/N = (Alesion/Mlesion) (Aliver/Mliver). This method is indicated in patients who have compromised hepatic functionality.
Another possible approach is voxel dosimetry, in which the calculation of the activity takes into account the biological damage required for tumor and healthy cells[5]. The final aim of this method, which is based on the evaluation of the real distribution, voxel by voxel, of the microspheres, simulated by 99mTc-MAA, is to treat the lesions with high doses, without overcoming the dose constraint to healthy liver, chosen for the single patient. Following this approach, it is possible to maximize the treatment of the lesion while limiting liver toxicity and thus giving the chance of a more specific and individualized cure to each patient[5].
The simulation by 99mTC-MAA is important not only to determine the dose delivered to the injected healthy liver, but also as a predictive factor. Garin et al[4] reported that quantitative 99mTC-MAA SPECT/CT is predictive of response to treatment, progression free survival (PFS) and overall survivial (OS), and has therefore a fundamental role in the selection of patients and the adaptation of treatment planning. The personalization of the activity planning could be further improved by using dual-tracer 99m Tc-MAA- 99m Tc-SC fusion SPECT, an imaging tool that merges data on radioactivity distribution with physiologic liver mapping that has been recently presented by Lam and colleagues[19].
Complications of radioembolization are either caused by delivering a toxic dose to non-tumoral tissues, or by procedural complications during the catheter’s placement and manipulation. The main complications include: (1) liver failure or radio-induced liver disease (RILD)[20,21], with an incidence up to 4%; (2) biliary complications[22] (incidence < 10%); (3) post-radioembolization syndrome (PRS), characterized by fatigue, nausea, vomiting, anorexia, fever, abdominal pain[23,24] (incidence 20%-55%); (4) gastrointestinal complications, with an incidence < 5% when an accurate angiographic phase is performed[25,26]; and (5) radio-induced pneumonia, whose incidence is < 1% if the hepato-pulmonary shunt is adequately calculated[27,28].
A careful and meticulous selection phase is crucial to reduce the incidence of complications. In addition, there is some consensus on the use of pre-medications to help prevent complications, such as proton pump inhibitors (starting one week before treatment and continuing for one month after the procedure), corticosteroids (for approximately 5 d from the interventions to reduce the incidence of PRS)[29], antiemetics and analgesics before the interventions and as needed.
Since radioembolization has only recently entered clinical practice, results from phase III clinical trials are still scant. As a consequence, radioembolization is not currently listed among possible treatment options for HCC in some guidelines such as those issued by the American Society of Clinical Oncology. However, other scientific societies such as the European Society of Medical Oncology consider radioembolization as a promising therapeutic option either as a “bridging” treatment or as the main therapy for patients with diffuse intrahepatic tumor spread[30]. In addition, the National Comprehensive Cancer Network guidelines consider radioembolization suitable for patients with unresectable disease due to inadequate hepatic reserve, poor performance status, comorbidities, or specific location and extension of the tumor[31]. Lastly, according to the National Cancer Institute (NCI) recommendations, radioembolization may be considered in selected patients with liver-confined HCC, who are not eligible for transplant or resection[32].
Thanks to its versatility, radioembolization has been evaluated in different clinical situations, as summarized in the following paragraphs.
Patients with early-stage (BCLC-A) HCC are candidates for curative treatments such as liver transplant. However, the low number of donors and the long waiting list expose patients to the risk of disease progression, with subsequent withdrawal from the waiting list.
Therefore, patients on the waiting list are frequently treated with locoregional approaches, such as percutaneous ablation or TACE, in order to limit the risk of local progression.
Recently, radioembolization has been proposed as a valuable therapeutic option for patients on the transplant waiting list[33], although this approach is not widely performed due to its procedural costs.
Patients with intermediate-stage (BCLC-B) HCC represent a very heterogeneous population[34,35]. TACE is usually considered the treatment of choice in this setting, although alternative loco-regional and medical (sorafenib) treatment do retain efficacy. In addition, the use of TACE is limited by a number of absolute and relative contraindications[36]. In this population of patients, radioembolization may be a viable therapeutic option, given the low incidence of associated adverse effects.
To date, no randomized trials have directly compared radioembolization and TACE in patients with intermediate-stage HCC, available data are therefore based mainly on retrospective assessments.
Salem et al[37] compared 123 patients treated with radioembolization with 122 subjects who had received TACE: overall, median time to progression - but not overall survival - was longer after radioembolization (13.3 mo vs 8.4 mo, P = 0.046), and this latter intervention was also associated with a more favorable safety profile. Similar results have been reported by other authors[38-41]. For instance, a very recent study by El Fouly et al[41] has shown that radioembolization presents a similar efficacy, but a lower incidence of adverse events and need for hospitalization when compared with TACE. From a healthcare-utilization perspective, radioembolization is definitely more complex and expensive than TACE; however, TACE requires more frequent, repeated treatments than radioembolization and may be associated with a less favorable safety profile, thus increasing indirect costs.
A retrospective analysis has also suggested that both radioembolization and sorafenib are effective in patients with intermediate-stage HCC, and are associated with a similar survival[42].
In the large population of intermediate-stage HCC patients, tumor shrinkage, or “downsizing” may convert the disease to surgical resectability or may offer the opportunity for transplant[43]. Several options, either percutaneous or trans-arterial, are now available to achieve tumor downsizing, and radioembolization has become part of this armamentarium.
A retrospective study has compared radioembolization and TACE for pre-transplant downsizing, and has shown that the percentage of tumor shrinkage was higher after radioembolization (58% vs 31%, P = 0.023)[44].
Radioembolization also represents a promising therapeutic option in patients with large extent of disease and insufficient residual liver volume, who are therefore not immediately eligible for surgery. In these patients, portal vein embolization (PVE) has been proposed to induce hypertrophy of the contralateral lobe and make surgical resection possible. However, PVE is associated with some risks of tumor progression within the liver lobe during hypertrophy. Radioembolization can induce a marked hypotrophy of the treated hepatic lobe, associated with an evident hypertrophy of the contralateral lobe (the so-called “radiation lobectomy”)[45]. Therefore, radioembolization has been proposed as an alternative to PVE in HCC patients. In addition, radioembolization offers the advantage of treating the cancer itself, thus reducing the risk of pre-interventional tumor progression, and represents a therapeutic option also in patients with neoplastic venous thrombosis[46]. Of note, 6-12 wk are necessary to achieve radiation lobectomy; during this time span, patients with more favorable biological tumor behavior and who may therefore gain most benefit from surgical resection can be identified[46].
Sorafenib represents the treatment of choice in patients with advanced stage (BCLC-C) HCC, and is associated with an overall survival of about 11 mo[47-50]. The overall survival associated with radioembolization in this setting ranges from 6 to 10 mo[9,10]; given its good safety profile, radioembolization might represent a potential alternative to sorafenib in selected patients who are not responding or do not tolerate this treatment. Of note, the preliminary results of the SORAMIC randomized trial, which compares radioembolization plus sorafenib with sorafenib alone in BCLC-C HCC patients, have shown that radioembolization followed by sorafenib appears to be as well tolerated as sorafenib alone[51].
Among patients with advanced HCC, radioembolization may provide the best outcome in subjects with PVT involving segmental or lobar branches, where the median overall survival has reached 17 mo with glass microspheres[37,52] and 23.2 mo using MAA SPECT/CT based dosimetry[53]. This compares with a median survival of 3-6 mo for patients with PVT of the common portal trunk. Less satisfactory results are documented for patients with distant metastases[12,54].
The therapeutic effects of radioembolization are evaluated mainly by the changes in the level of tumor markers and by radiological findings[55,56].
Tumor markers, in particular α-fetoprotein, are usually non-specific[57]. A decrease of α-fetoprotein may suggest a good response to treatment, but its increase does not provide any well-grounded clinical indication, as it can be determined not only by tumor progression, but also by lithic phenomena, infectious diseases or changes in liver function.
Imaging therefore becomes paramount to evaluate the response to treatment and therefore guide therapeutic choices. To this end, the American Association for the Study of Liver Diseases has proposed the “mRECIST criteria”[58]: according to mRECIST, the response to a given treatment is evaluated according to the reduction of the diameter of vital residual portion. These criteria have been shown to be accurate in identifying the complete necrosis of tumor mass after radioembolization[59]. However, post-radioembolization diagnostics still remain an open issue, especially in patients with partial response or stable disease - which represent the majority of cases. In fact, tumor necrosis is often irregular in distribution and contrast enhancement, making it difficult to measure vital portions. Therefore, the routine use of volumetric measurements of tumor necrosis have been proposed as a more accurate, reproducible and sensitive method for the early identification of responding patients[60,61].
The optimal time for the evaluation of treatment response is also debated. Although the first dimensional changes may already be observed after 1 mo, it is widely accepted that at least 3 to 4 mo are necessary to reliably estimate the actual response and therefore evaluate whether re-treatment may be considered.
Radioembolization represents a feasible and promising therapy for the treatment of all stages of HCC. Although it is technically complex and expensive, radioembolization may represent a valid alternative to TACE in intermediate-stage HCC and may be a suitable companion to sorafenib in advanced HCC.
P- Reviewer: Xu Y S- Editor: Yu J L- Editor: Logan S E- Editor: Wang CH
| 1. | El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557-2576. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 3846] [Cited by in F6Publishing: 4183] [Article Influence: 246.1] [Reference Citation Analysis (2)] |
| 2. | Ozenne V, Bouattour M, Goutté N, Vullierme MP, Ripault MP, Castelnau C, Valla DC, Degos F, Farges O. Prospective evaluation of the management of hepatocellular carcinoma in the elderly. Dig Liver Dis. 2011;43:1001-1005. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 19] [Cited by in F6Publishing: 18] [Article Influence: 1.4] [Reference Citation Analysis (0)] |
| 3. | Sangro B, Salem R, Kennedy A, Coldwell D, Wasan H. Radioembolization for hepatocellular carcinoma: a review of the evidence and treatment recommendations. Am J Clin Oncol. 2011;34:422-431. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 69] [Cited by in F6Publishing: 81] [Article Influence: 6.2] [Reference Citation Analysis (0)] |
| 4. | Garin E, Lenoir L, Rolland Y, Edeline J, Mesbah H, Laffont S, Porée P, Clément B, Raoul JL, Boucher E. Dosimetry based on 99mTc-macroaggregated albumin SPECT/CT accurately predicts tumor response and survival in hepatocellular carcinoma patients treated with 90Y-loaded glass microspheres: preliminary results. J Nucl Med. 2012;53:255-263. [PubMed] [DOI] [Cited in This Article: ] [Cited by in F6Publishing: 1] [Reference Citation Analysis (0)] |
| 5. | Chiesa C, Maccauro M, Romito R, Spreafico C, Pellizzari S, Negri A, Sposito C, Morosi C, Civelli E, Lanocita R. Need, feasibility and convenience of dosimetric treatment planning in liver selective internal radiation therapy with (90)Y microspheres: the experience of the National Tumor Institute of Milan. Q J Nucl Med Mol Imaging. 2011;55:168-197. [PubMed] [Cited in This Article: ] |
| 6. | Lau WY, Kennedy AS, Kim YH, Lai HK, Lee RC, Leung TW, Liu CS, Salem R, Sangro B, Shuter B. Patient selection and activity planning guide for selective internal radiotherapy with yttrium-90 resin microspheres. Int J Radiat Oncol Biol Phys. 2012;82:401-407. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 160] [Cited by in F6Publishing: 160] [Article Influence: 11.4] [Reference Citation Analysis (0)] |
| 7. | Ariel IM, Pack GT. Treatment of inoperable cancer of the liver by intra-arterial radioactive isotopes and chemotherapy. Cancer. 1967;20:793-804. [PubMed] [Cited in This Article: ] |
| 8. | Blanchard RJ, Grotenhuis I, Lafave JW, Frye CW, Perry JF. Treatment of experimental tumors; utilization of radioactive microspheres. Arch Surg. 1964;89:406-410. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 30] [Cited by in F6Publishing: 32] [Article Influence: 1.1] [Reference Citation Analysis (0)] |
| 9. | Salem R, Lewandowski RJ, Mulcahy MF, Riaz A, Ryu RK, Ibrahim S, Atassi B, Baker T, Gates V, Miller FH. Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes. Gastroenterology. 2010;138:52-64. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 29] [Cited by in F6Publishing: 32] [Article Influence: 3.2] [Reference Citation Analysis (0)] |
| 10. | Sangro B, Carpanese L, Cianni R, Golfieri R, Gasparini D, Ezziddin S, Paprottka PM, Fiore F, Van Buskirk M, Bilbao JI. Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation. Hepatology. 2011;54:868-878. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 464] [Cited by in F6Publishing: 483] [Article Influence: 37.2] [Reference Citation Analysis (0)] |
| 11. | Hilgard P, Hamami M, Fouly AE, Scherag A, Müller S, Ertle J, Heusner T, Cicinnati VR, Paul A, Bockisch A. Radioembolization with yttrium-90 glass microspheres in hepatocellular carcinoma: European experience on safety and long-term survival. Hepatology. 2010;52:1741-1749. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 316] [Cited by in F6Publishing: 339] [Article Influence: 24.2] [Reference Citation Analysis (0)] |
| 12. | Kulik LM, Carr BI, Mulcahy MF, Lewandowski RJ, Atassi B, Ryu RK, Sato KT, Benson A, Nemcek AA, Gates VL. Safety and efficacy of 90Y radiotherapy for hepatocellular carcinoma with and without portal vein thrombosis. Hepatology. 2008;47:71-81. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 447] [Cited by in F6Publishing: 436] [Article Influence: 27.3] [Reference Citation Analysis (0)] |
| 13. | Bester L, Meteling B, Boshell D, Chua TC, Morris DL. Transarterial chemoembolisation and radioembolisation for the treatment of primary liver cancer and secondary liver cancer: a review of the literature. J Med Imaging Radiat Oncol. 2014;58:341-352. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 31] [Cited by in F6Publishing: 38] [Article Influence: 3.8] [Reference Citation Analysis (0)] |
| 14. | Covey AM, Brody LA, Maluccio MA, Getrajdman GI, Brown KT. Variant hepatic arterial anatomy revisited: digital subtraction angiography performed in 600 patients. Radiology. 2002;224:542-547. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 253] [Cited by in F6Publishing: 214] [Article Influence: 9.7] [Reference Citation Analysis (0)] |
| 15. | Ilhan H, Goritschan A, Paprottka P, Jakobs TF, Fendler WP, Bartenstein P, Hacker M, Haug AR. Systematic evaluation of tumoral 99mTc-MAA uptake using SPECT and SPECT/CT in 502 patients before 90Y radioembolization. J Nucl Med. 2015;56:333-338. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 16] [Cited by in F6Publishing: 18] [Article Influence: 2.0] [Reference Citation Analysis (0)] |
| 16. | Ho S, Lau WY, Leung TW, Chan M, Johnson PJ, Li AK. Clinical evaluation of the partition model for estimating radiation doses from yttrium-90 microspheres in the treatment of hepatic cancer. Eur J Nucl Med. 1997;24:293-298. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 27] [Cited by in F6Publishing: 64] [Article Influence: 2.4] [Reference Citation Analysis (0)] |
| 17. | MDS Nordion. TheraSphere® Yttrium-90 Glass Microspheres US package insert. US: MDS Nordion 2007; . [Cited in This Article: ] |
| 18. | Sirtex Medical. IR-Spheres® training program: physicians and institutions. Lane Cove: Sirtex Medical; . [Cited in This Article: ] |
| 19. | Lam MG, Goris ML, Iagaru AH, Mittra ES, Louie JD, Sze DY. Prognostic utility of 90Y radioembolization dosimetry based on fusion 99mTc-macroaggregated albumin-99mTc-sulfur colloid SPECT. J Nucl Med. 2013;54:2055-2061. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 50] [Cited by in F6Publishing: 54] [Article Influence: 4.9] [Reference Citation Analysis (0)] |
| 20. | Jakobs TF, Saleem S, Atassi B, Reda E, Lewandowski RJ, Yaghmai V, Miller F, Ryu RK, Ibrahim S, Sato KT. Fibrosis, portal hypertension, and hepatic volume changes induced by intra-arterial radiotherapy with 90yttrium microspheres. Dig Dis Sci. 2008;53:2556-2563. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 106] [Cited by in F6Publishing: 110] [Article Influence: 6.9] [Reference Citation Analysis (0)] |
| 21. | Sangro B, Gil-Alzugaray B, Rodriguez J, Sola I, Martinez-Cuesta A, Viudez A, Chopitea A, Iñarrairaegui M, Arbizu J, Bilbao JI. Liver disease induced by radioembolization of liver tumors: description and possible risk factors. Cancer. 2008;112:1538-1546. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 263] [Cited by in F6Publishing: 256] [Article Influence: 16.0] [Reference Citation Analysis (0)] |
| 22. | Atassi B, Bangash AK, Lewandowski RJ, Ibrahim S, Kulik L, Mulcahy MF, Murthy R, Ryu RK, Sato KT, Miller FH. Biliary sequelae following radioembolization with Yttrium-90 microspheres. J Vasc Interv Radiol. 2008;19:691-697. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 114] [Cited by in F6Publishing: 131] [Article Influence: 8.2] [Reference Citation Analysis (0)] |
| 23. | Kennedy AS, Coldwell D, Nutting C, Murthy R, Wertman DE, Loehr SP, Overton C, Meranze S, Niedzwiecki J, Sailer S. Resin 90Y-microsphere brachytherapy for unresectable colorectal liver metastases: modern USA experience. Int J Radiat Oncol Biol Phys. 2006;65:412-425. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 283] [Cited by in F6Publishing: 265] [Article Influence: 14.7] [Reference Citation Analysis (0)] |
| 24. | Murthy R, Xiong H, Nunez R, Cohen AC, Barron B, Szklaruk J, Madoff DC, Gupta S, Wallace MJ, Ahrar K. Yttrium 90 resin microspheres for the treatment of unresectable colorectal hepatic metastases after failure of multiple chemotherapy regimens: preliminary results. J Vasc Interv Radiol. 2005;16:937-945. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 123] [Cited by in F6Publishing: 115] [Article Influence: 6.1] [Reference Citation Analysis (0)] |
| 25. | Murthy R, Brown DB, Salem R, Meranze SG, Coldwell DM, Krishnan S, Nunez R, Habbu A, Liu D, Ross W. Gastrointestinal complications associated with hepatic arterial Yttrium-90 microsphere therapy. J Vasc Interv Radiol. 2007;18:553-561; quiz 562. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 128] [Cited by in F6Publishing: 121] [Article Influence: 7.1] [Reference Citation Analysis (0)] |
| 26. | Szyszko T, Al-Nahhas A, Tait P, Rubello D, Canelo R, Habib N, Jiao L, Wasan H, Bansi D, Thillainayagam A. Management and prevention of adverse effects related to treatment of liver tumours with 90Y microspheres. Nucl Med Commun. 2007;28:21-24. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 31] [Cited by in F6Publishing: 29] [Article Influence: 1.7] [Reference Citation Analysis (0)] |
| 27. | Leung TW, Lau WY, Ho SK, Ward SC, Chow JH, Chan MS, Metreweli C, Johnson PJ, Li AK. Radiation pneumonitis after selective internal radiation treatment with intraarterial 90yttrium-microspheres for inoperable hepatic tumors. Int J Radiat Oncol Biol Phys. 1995;33:919-924. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 236] [Cited by in F6Publishing: 216] [Article Influence: 7.4] [Reference Citation Analysis (0)] |
| 28. | Salem R, Parikh P, Atassi B, Lewandowski RJ, Ryu RK, Sato KT, Gates VL, Ibrahim S, Mulcahy MF, Kulik L. Incidence of radiation pneumonitis after hepatic intra-arterial radiotherapy with yttrium-90 microspheres assuming uniform lung distribution. Am J Clin Oncol. 2008;31:431-438. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 119] [Cited by in F6Publishing: 121] [Article Influence: 7.6] [Reference Citation Analysis (0)] |
| 29. | 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;17:1251-1278. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 491] [Cited by in F6Publishing: 481] [Article Influence: 26.7] [Reference Citation Analysis (0)] |
| 30. | Jelic S, Sotiropoulos GC. Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21 Suppl 5:v59-v64. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 130] [Cited by in F6Publishing: 156] [Article Influence: 11.1] [Reference Citation Analysis (0)] |
| 31. | National comprehensive cancer network clinical practice guidelines in oncology. Hepatobiliary guidelines. V2.2010. Available from: http://www.nccn.org/professionals/physician_gls/PDF/hepatobiliary.pdf. [Cited in This Article: ] |
| 32. | Thomas MB, Jaffe D, Choti MM, Belghiti J, Curley S, Fong Y, Gores G, Kerlan R, Merle P, O’Neil B. Hepatocellular carcinoma: consensus recommendations of the National Cancer Institute Clinical Trials Planning Meeting. J Clin Oncol. 2010;28:3994-4005. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 280] [Cited by in F6Publishing: 315] [Article Influence: 22.5] [Reference Citation Analysis (1)] |
| 33. | Kulik LM, Atassi B, van Holsbeeck L, Souman T, Lewandowski RJ, Mulcahy MF, Hunter RD, Nemcek AA, Abecassis MM, Haines KG. Yttrium-90 microspheres (TheraSphere) treatment of unresectable hepatocellular carcinoma: downstaging to resection, RFA and bridge to transplantation. J Surg Oncol. 2006;94:572-586. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 249] [Cited by in F6Publishing: 236] [Article Influence: 13.1] [Reference Citation Analysis (0)] |
| 34. | Lencioni R. Loco-regional treatment of hepatocellular carcinoma. Hepatology. 2010;52:762-773. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 364] [Cited by in F6Publishing: 391] [Article Influence: 27.9] [Reference Citation Analysis (0)] |
| 35. | Piscaglia F, Bolondi L. The intermediate hepatocellular carcinoma stage: Should treatment be expanded? Dig Liver Dis. 2010;42 Suppl 3:S258-S263. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 42] [Cited by in F6Publishing: 39] [Article Influence: 2.8] [Reference Citation Analysis (0)] |
| 36. | Raoul JL, Sangro B, Forner A, Mazzaferro V, Piscaglia F, Bolondi L, Lencioni R. Evolving strategies for the management of intermediate-stage hepatocellular carcinoma: available evidence and expert opinion on the use of transarterial chemoembolization. Cancer Treat Rev. 2011;37:212-220. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 365] [Cited by in F6Publishing: 411] [Article Influence: 29.4] [Reference Citation Analysis (0)] |
| 37. | Salem R, Lewandowski RJ, Kulik L, Wang E, Riaz A, Ryu RK, Sato KT, Gupta R, Nikolaidis P, Miller FH. Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology. 2011;140:497-507.e2. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 451] [Cited by in F6Publishing: 488] [Article Influence: 37.5] [Reference Citation Analysis (0)] |
| 38. | Kooby DA, Egnatashvili V, Srinivasan S, Chamsuddin A, Delman KA, Kauh J, Staley CA, Kim HS. Comparison of yttrium-90 radioembolization and transcatheter arterial chemoembolization for the treatment of unresectable hepatocellular carcinoma. J Vasc Interv Radiol. 2010;21:224-230. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 135] [Cited by in F6Publishing: 143] [Article Influence: 9.5] [Reference Citation Analysis (0)] |
| 39. | Carr BI, Kondragunta V, Buch SC, Branch RA. Therapeutic equivalence in survival for hepatic arterial chemoembolization and yttrium 90 microsphere treatments in unresectable hepatocellular carcinoma: a two-cohort study. Cancer. 2010;116:1305-1314. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 131] [Cited by in F6Publishing: 143] [Article Influence: 10.2] [Reference Citation Analysis (0)] |
| 40. | Moreno-Luna LE, Yang JD, Sanchez W, Paz-Fumagalli R, Harnois DM, Mettler TA, Gansen DN, de Groen PC, Lazaridis KN, Narayanan Menon KV. Efficacy and safety of transarterial radioembolization versus chemoembolization in patients with hepatocellular carcinoma. Cardiovasc Intervent Radiol. 2013;36:714-723. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 93] [Cited by in F6Publishing: 108] [Article Influence: 9.0] [Reference Citation Analysis (0)] |
| 41. | El Fouly A, Ertle J, El Dorry A, Shaker MK, Dechêne A, Abdella H, Mueller S, Barakat E, Lauenstein T, Bockisch A. In intermediate stage hepatocellular carcinoma: radioembolization with yttrium 90 or chemoembolization? Liver Int. 2015;35:627-635. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 66] [Cited by in F6Publishing: 73] [Article Influence: 8.1] [Reference Citation Analysis (0)] |
| 42. | Gramenzi A, Golfieri R, Mosconi C, Cappelli A, Granito A, Cucchetti A, Marinelli S, Pettinato C, Erroi V, Fiumana S. Yttrium-90 radioembolization vs sorafenib for intermediate-locally advanced hepatocellular carcinoma: a cohort study with propensity score analysis. Liver Int. 2015;35:1036-1047. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 80] [Cited by in F6Publishing: 86] [Article Influence: 9.6] [Reference Citation Analysis (0)] |
| 43. | Iñarrairaegui M, Pardo F, Bilbao JI, Rotellar F, Benito A, D’Avola D, Herrero JI, Rodriguez M, Martí P, Zozaya G. Response to radioembolization with yttrium-90 resin microspheres may allow surgical treatment with curative intent and prolonged survival in previously unresectable hepatocellular carcinoma. Eur J Surg Oncol. 2012;38:594-601. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 81] [Cited by in F6Publishing: 84] [Article Influence: 7.0] [Reference Citation Analysis (0)] |
| 44. | Lewandowski RJ, Kulik LM, Riaz A, Senthilnathan S, Mulcahy MF, Ryu RK, Ibrahim SM, Sato KT, Baker T, Miller FH. A comparative analysis of transarterial downstaging for hepatocellular carcinoma: chemoembolization versus radioembolization. Am J Transplant. 2009;9:1920-1928. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 408] [Cited by in F6Publishing: 423] [Article Influence: 28.2] [Reference Citation Analysis (0)] |
| 45. | Vouche M, Lewandowski RJ, Atassi R, Memon K, Gates VL, Ryu RK, Gaba RC, Mulcahy MF, Baker T, Sato K. Radiation lobectomy: time-dependent analysis of future liver remnant volume in unresectable liver cancer as a bridge to resection. J Hepatol. 2013;59:1029-1036. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 170] [Cited by in F6Publishing: 202] [Article Influence: 18.4] [Reference Citation Analysis (0)] |
| 46. | Gaba RC, Lewandowski RJ, Kulik LM, Riaz A, Ibrahim SM, Mulcahy MF, Ryu RK, Sato KT, Gates V, Abecassis MM. Radiation lobectomy: preliminary findings of hepatic volumetric response to lobar yttrium-90 radioembolization. Ann Surg Oncol. 2009;16:1587-1596. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 159] [Cited by in F6Publishing: 174] [Article Influence: 11.6] [Reference Citation Analysis (0)] |
| 47. | Galle P, Blanc J, Van Laethem JL. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma and prior antitumor therapy: a subanalysis from the SHARP trial. J Hepatol. 2008;20:S372. [DOI] [Cited in This Article: ] |
| 48. | Bruix J, Raoul JL, Sherman M, Mazzaferro V, Bolondi L, Craxi A, Galle PR, Santoro A, Beaugrand M, Sangiovanni A. Efficacy and safety of sorafenib in patients with hepatocellular carcinoma (HCC): subanalysis of Sharp trial based on Barcelona Clinic Liver Cancer (BCLC) stage. J Hepatol. 2009;50:S28. [DOI] [Cited in This Article: ] [Cited by in Crossref: 565] [Cited by in F6Publishing: 621] [Article Influence: 51.8] [Reference Citation Analysis (0)] |
| 49. | Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10:25-34. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 3854] [Cited by in F6Publishing: 4486] [Article Influence: 280.4] [Reference Citation Analysis (0)] |
| 50. | Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378-390. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 9016] [Cited by in F6Publishing: 9880] [Article Influence: 617.5] [Reference Citation Analysis (2)] |
| 51. | Ricke J, Bulla K, Kolligs F, Peck-Radosavljevic M, Reimer P, Sangro B, Schott E, Schütte K, Verslype C, Walecki J. Safety and toxicity of radioembolization plus Sorafenib in advanced hepatocellular carcinoma: analysis of the European multicentre trial SORAMIC. Liver Int. 2015;35:620-626. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 64] [Cited by in F6Publishing: 70] [Article Influence: 7.8] [Reference Citation Analysis (0)] |
| 52. | Mazzaferro V, Sposito C, Bhoori S, Romito R, Chiesa C, Morosi C, Maccauro M, Marchianò A, Bongini M, Lanocita R. Yttrium-90 radioembolization for intermediate-advanced hepatocellular carcinoma: a phase 2 study. Hepatology. 2013;57:1826-1837. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 340] [Cited by in F6Publishing: 381] [Article Influence: 34.6] [Reference Citation Analysis (0)] |
| 53. | Garin E, Lenoir L, Edeline J, Laffont S, Mesbah H, Porée P, Sulpice L, Boudjema K, Mesbah M, Guillygomarc’h A. Boosted selective internal radiation therapy with 90Y-loaded glass microspheres (B-SIRT) for hepatocellular carcinoma patients: a new personalized promising concept. Eur J Nucl Med Mol Imaging. 2013;40:1057-1068. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 158] [Cited by in F6Publishing: 148] [Article Influence: 13.5] [Reference Citation Analysis (0)] |
| 54. | Woodall CE, Scoggins CR, Ellis SF, Tatum CM, Hahl MJ, Ravindra KV, McMasters KM, Martin RC. Is selective internal radioembolization safe and effective for patients with inoperable hepatocellular carcinoma and venous thrombosis? J Am Coll Surg. 2009;208:375-382. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 44] [Cited by in F6Publishing: 56] [Article Influence: 3.7] [Reference Citation Analysis (0)] |
| 55. | Atassi B, Bangash AK, Bahrani A, Pizzi G, Lewandowski RJ, Ryu RK, Sato KT, Gates VL, Mulcahy MF, Kulik L. Multimodality imaging following 90Y radioembolization: a comprehensive review and pictorial essay. Radiographics. 2008;28:81-99. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 106] [Cited by in F6Publishing: 106] [Article Influence: 6.6] [Reference Citation Analysis (0)] |
| 56. | Riaz A, Ryu RK, Kulik LM, Mulcahy MF, Lewandowski RJ, Minocha J, Ibrahim SM, Sato KT, Baker T, Miller FH. Alpha-fetoprotein response after locoregional therapy for hepatocellular carcinoma: oncologic marker of radiologic response, progression, and survival. J Clin Oncol. 2009;27:5734-5742. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 165] [Cited by in F6Publishing: 176] [Article Influence: 11.7] [Reference Citation Analysis (0)] |
| 57. | Chan SL, Mo FK, Johnson PJ, Hui EP, Ma BB, Ho WM, Lam KC, Chan AT, Mok TS, Yeo W. New utility of an old marker: serial alpha-fetoprotein measurement in predicting radiologic response and survival of patients with hepatocellular carcinoma undergoing systemic chemotherapy. J Clin Oncol. 2009;27:446-452. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 186] [Cited by in F6Publishing: 208] [Article Influence: 13.0] [Reference Citation Analysis (0)] |
| 58. | Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010;30:52-60. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 2583] [Cited by in F6Publishing: 3092] [Article Influence: 220.9] [Reference Citation Analysis (36)] |
| 59. | Riaz A, Kulik L, Lewandowski RJ, Ryu RK, Giakoumis Spear G, Mulcahy MF, Abecassis M, Baker T, Gates V, Nayar R. Radiologic-pathologic correlation of hepatocellular carcinoma treated with internal radiation using yttrium-90 microspheres. Hepatology. 2009;49:1185-1193. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 204] [Cited by in F6Publishing: 200] [Article Influence: 13.3] [Reference Citation Analysis (0)] |
| 60. | Monsky WL, Garza AS, Kim I, Loh S, Lin TC, Li CS, Fisher J, Sandhu P, Sidhar V, Chaudhari AJ. Treatment planning and volumetric response assessment for Yttrium-90 radioembolization: semiautomated determination of liver volume and volume of tumor necrosis in patients with hepatic malignancy. Cardiovasc Intervent Radiol. 2011;34:306-318. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 25] [Cited by in F6Publishing: 21] [Article Influence: 1.5] [Reference Citation Analysis (0)] |
| 61. | Galizia MS, Töre HG, Chalian H, McCarthy R, Salem R, Yaghmai V. MDCT necrosis quantification in the assessment of hepatocellular carcinoma response to yttrium 90 radioembolization therapy: comparison of two-dimensional and volumetric techniques. Acad Radiol. 2012;19:48-54. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 20] [Cited by in F6Publishing: 24] [Article Influence: 2.0] [Reference Citation Analysis (0)] |