Complete eradication of hepatic metastasis from colorectal cancer by Yttrium-90 SIRT

Yttrium-90 (Y-90) radioembolization,also known as selective internal radiation therapy (SIRT),is a regional hepatic therapy used in the treatment of unresectable colorectal cancer (CRC) liver metastases. In SIRT,Y-90 impregnated microspheres are injected into the VASCULAR SUPPLY of hepatic tumor,leading to selective irradiation and necrosis of tumor TISSUE. While several studies demonstrate improved local control and survival with SIRT,the specific indications for this therapy have yet to be defined. Typically,SIRT is given in combination with chemotherapy as multimodal treatment for unresectable hepatic CRC. However,it HAS ALSO FOUND INCREASING USE as a salvage therapy in chemo-refractory patients. Herein,the authors describe their experience with SIRT as "stand alone" therapy in a surgically-prohibitive,chemotherapy naive patient with hepatic CRC metastasis. The results suggest that Y-90 SIRT may have potential applications beyond its usual role as a palliative or salvage therapy for unresectable hepatic CRC.     

Role of radiation therapy in gastric adenocarcinoma

Outcomes in patients with gastric cancer in the United States remain disappointing, with a five-year overall survival rate of approximately 23%. Given high rates of local-regional control following surgery, a strong rationale exists for the use of adjuvant radiation therapy. Randomized trials have shown superior local control with adjuvant radiotherapy and improved overall survival with adjuvant chemoradiation. The benefit of adjuvant chemoradiation in patients who have undergone D2 lymph node dissection by an experienced surgeon is not known, and the benefit of adjuvant radiation therapy in addition to adjuvant chemotherapy continues to be defined. In unresectable disease, chemoradiation allows long-term survival in a small number of patients and provides effective palliation. Most trials show a benefit to combined modality therapy compared to chemotherapy or radiation therapy alone. The use of pre-operative, intra-operative, 3D conformal, and intensity modulated radiation therapy in gastric cancer is promising but requires further study. The current article reviews the role of radiation therapy in the treatment of resectable and unresectable gastric carcinoma, focusing on current recommendations in the United States.     

Interventional treatment for unresectable hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is the sixth most common cancer and third leading cause of cancer-related death in the world. The Barcelona clinic liver cancer classification is the current standard classification system for the clinical management of patients with HCC and suggests that patients with intermediate-stage HCC benefit from transcatheter arterial chemoembolization(TACE). Interventional treatments such as TACE, balloon-occluded TACE, drug-eluting bead embolization, radioembolization, and combined therapies including TACE and radiofrequency ablation, continue to evolve, resulting in improved patient prognosis. However, patients with advanced-stage HCC typically receive only chemotherapy with sorafenib, a multi-kinase inhibitor, or palliative and conservative therapy. Most patients receive palliative or conservative therapy only, and approximately 50% of patients with HCC are candidatesfor systemic therapy. However, these patients require therapy that is more effective than sorafenib or conservative treatment. Several researchers try to perform more effective therapies, such as combined therapies(TACE with radiotherapy and sorafenib with TACE), modified TACE for HCC with arterioportal or arteriohepatic vein shunts, TACE based on hepatic hemodynamics, and isolated hepatic perfusion. This review summarizes the published data and data on important ongoing studies concerning interventional treatments for unresectable HCC and discusses the technical improvements in these interventions, particularly for advanced-stage HCC.     

Immunotherapy for colorectal cancer

The incidence of colorectal cancer(CRC)is on the rise,and the prognosis for patients with recurrent or metastatic disease is extremely poor.Although chemotherapy and radiation therapy can improve survival rates,it is imperative to integrate alternative strategies such as immunotherapy to improve outcomes for patients with advanced CRC.In this review,we will discuss the effect of immunotherapy for inducing cytotoxic T lymphocytes and the major immunotherapeutic approaches for CRC that are currently in clinical trials,including peptide vaccines,dendritic cell-based cancer vaccines,whole tumor cell vaccines,viral vector-based cancer vaccines,adoptive cell transfer therapy,antibody-based cancer immunotherapy,and cytokine therapy.The possibility of combination therapies will also be discussed along with the challenges presented by tumor escape mechanisms.     

Hepatitis B virus reactivation in patients with hepatocellular carcinoma undergoing anti-cancer therapy

Patients with hepatocellular carcinoma(HCC)often experience hepatic morbidity.Hepatitis B virus(HBV)reactivation is well documented as a serious hepatic morbidity during anti-cancer therapy.Reported rates of HBV reactivation in chronic carriers with HCC undergoing chemotherapy range from 4%-67%.Apart from chemotherapy,HBV reactivation has been increasingly identified in settings of hepatectomy and local ablation therapies.The rates of HBV reactivation vary with different levels of immunosuppression and depend on treatment,viral factors,and patient characteristics.The principal concern relating to reactivation is that a substantial proportion of patients with reactivation suffer from liver dysfunction during therapy,which often leads to disruption of planned,potentially life-prolonging treatments,adversely affecting the patients’final outcome.The first step in the management of HBV reactivation is identification of patients at risk of reactivation by testing for HBV serology prior to commencing anticancer therapy.Although it is a serious complication,HBV reactivation is preventable with prophylactic antiHBV drugs.Multiple publications have shown the benefit of prophylactic or preemptive antiviral therapy in this setting and justified such an approach before the start of therapy.Given the tumors and underlying cirrhosis,long-term use of antivirals with high potency and low risk of resistance is recommended in patients with HCC.This topic review will summarize the epidemiology,pathogenesis,and clinical issues related to HBV reactivation in HCC patients,and will discuss proper management against HBV reactivation during anti-cancer therapy for HCC.     

Radiofrequency ablation or percutaneous ethanol injection for the treatment of liver tumors

The liver is a common location of both primary and secondary malignancies. For unresectable liver cancer, many local ablative therapies have been developed. These include e.g., percutaneous ethanol injection (PEI), percutaneous acetic acid injection, radiofrequency ablation (RFA), cryoablation, microwave ablation, laserinduced thermotherapy, and high-intensity focused ultrasound. RFA has recently gained interest and is the most widely applied thermoablative technique. RFA allows more effective tumor control in fewer treatment sessions compared with PEI, but with a higher rate of complications. However, there are certain circumstances where PEI therapy represents a better strategy to control liver tumors than RFA, especially in situations where RFA is difficult, for example when large vessels surround the tumor. In the context of hepatocellular carcinoma (HCC), both RFA and PEI are feasible and of benefit in non-operable patients. RFA seems superior to PEI in HCC 2 cm, and the combination of interventions may be of benefit in selected patients. Liver resection is superior to RFA for patients with HCC meeting the Milan criteria, but RFA can be employed in tumors ≤ 3 cm and where there is an increased expected operative mortality. In addition, some lines of evidence indicate that RFA and PEI can be employed as a bridge to liver transplantation. The use of RFA in colorectal liver metastases is currently limited to unresectable disease and for patients unfit for surgery. The aim of this article is to summarize the current status of RFA in the management of liver tumors and compare it to the cheap and readily available technique of PEI.     

Recent advances in multidisciplinary management of hepatocellular carcinoma

The incidence of hepatocellular carcinoma(HCC) is increasing, and it is currently the second leading cause of cancer-related death worldwide. Potentially curative treatment options for HCC include resection, transplantation, and percutaneous ablation, whereas palliative treatments include trans-arterial chemoembolization(TACE), radioembolization, and systemic treatments. Due to the diversity of available treatment options and patients’ presentations, a multidisciplinaryteam should decide clinical management of HCC, according to tumor characteristics and stage of liver disease. Potentially curative treatments are suitable for very-early- and early-stage HCC. However, the vast majority of HCC patients are diagnosed in later stages, where the tumor characteristics or progress of liver disease prevent curative interventions. For patients with intermediate-stage HCC, TACE and radioembolization improve survival and are being evaluated in addition to potentially curative therapies or with systemic targeted therapy. There is currently no effective systemic chemotherapy, immunologic, or hormonal therapy for HCC, and sorafenib is the only approved moleculartargeted treatment for advanced HCC. Other targeted agents are under investigation; trials comparing new agents in combination with sorafenib are ongoing. Combinations of systemic targeted therapies with local treatments are being evaluated for further improvements in HCC patient outcomes. This article provides an updated and comprehensive overview of the current standards and trends in the treatment of HCC.     

One case of intrahepatic cholangiocarcinoma amenable to resection after radioembolization

We report the case of a 57-year-old man who was diagnosed with a large unresectable cholangiocarcinoma associated with 2 satellite nodules and without clear margins with the right hepatic vein.Despite 4 cycles of GEMOX(stopped due to a hypertransaminasemia believed to be due to gemcitabine)and 4 cycles of FOLFIRINOX,the tumor remained stable and continued to be considered unresectable.Radioembolization(resin microspheres,SIRS-spheres)targeting the left liver(474 MBq)and segment IV(440 MBq)was performed.This injection was very well tolerated,and 4 more cycles of FOLFIRINOX were given while waiting for radioembolization efficacy.On computed tomography scan,a partial response was observed;the tumor was far less hypervascularized,and a margin was observed between the tumor and the right hepatic vein.A left hepatectomy enlarged to segmentⅧwas performed.On pathological exam,most of the tumor was acellular,with dense fibrosis around visible microspheres.Viable cells were observed only at a distance from beads.Radioembolization can be useful in the treatment of cholangiocarcinoma,allowing in some cases a secondary resection.     

Image-guided therapies in the treatment of hepatocellular carcinoma: A multidisciplinary perspective

A multidisciplinary approach to the treatment of patients with unresectable hepatocellular carcinoma(HCC) has led to improvements in screening, detection,and treatments. Interventional techniques includethermal ablation, transarterial chemoembolization, and radioembolization whilst stereotactic body radiation therapy also uses imaging to target the radiation. Both survival rates and cure rates have improved markedly since the introduction of these techniques. This review article describes the image guided techniques used for the treatment of HCC.     

Local injection therapy for hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world and ranks the third most common cause of cancer-related death. Surgical resection, liver transplantation and percutaneous ablation are generally considered the only curative treatment for early stage HCC. Besides the limitations of insufficient organ donors and a long waiting time for liver transplantation, however, resection is applied only to patients with good hepatic reserve and localized tumors, with a resectability of 30%. DATA SOURCES: Local ablation therapy, which is minimally invasive but contributes to the significant improvement of survival in patients with unresectable tumor, hasbeen widely used in treating small HCC. Among the techniques of local therapy, percutaneous ethanol injection (PEI) with a complete response in 80% of HCCs less than 3 cm has been accepted as an alternative to surgery in patients with small HCC. Moreover, percutaneous hepatic quantified ethanol injection (PHQEI) or PEI according to the standard criteria has been confirmed to benefit patients with HCC, especially when quantified ethanol is given at a short interval (QESI, the interval was 2-3 days). RESULT: Several limitations related to local percutaneous methods may result in incomplete therapeutic effect in case of larger HCC nodules (>3 cm). CONCLUSION: The combined use of different methods according to the clinical status of patients or tumors may be essential to the effective treatment of HCC.     

Radioembolization for Hepatocellular Carcinoma using TheraSphere?

Background/Aim:

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. Radioembolization with yttrium-90 (Y90) microspheres is a new concept in radiation therapy for HCC. This review focuses on the indications, efficacy, side effects, and future direction of Y90 therapy, using TheraSphere^®, in HCC patients.

Results:

Comprehensive literature reviews have described the clinical and scientific evidence of Y90 therapy. The Radioembolization Brachytherapy Oncology Consortium has concluded that there is sufficient evidence to support the safe and effective use of this locoregional therapy in HCC patients, including those with portal vein thrombosis.

Conclusions:

There are currently no randomized clinical trials done on TheraSphere^® and none of the studies so far have shown a survival benefit. Thus, although it represents a very promising therapy with excellent initial results, it cannot be fully recommended yet, till well-designed, large, randomized clinical studies are conducted showing survival benefits.     

Effects of Yttrium-90 selective internal radiation therapy on non-conventional liver tumors

The liver is a common site of metastasis, with essentially all metastatic malignancies having been known to spread to the liver. Nearly half of all patients with extrahepatic primary cancer have hepatic metastases. The severe prognostic implications of hepatic metastases have made surgical resection an important first line treatment in management. However, limitations such as the presence of extrahepatic spread or poor functional hepatic reserve exclude the majority of patients as surgical candidates, leaving chemotherapy and locoregional therapies as next best options. Selective internal radiation therapy (SIRT) is a form of catheter-based locoregional cancer treatment modality for unresectable tumors, involving trans-arterial injection of microspheres embedded with a radio-isotope Yttrium-90. The therapeutic radiation dose is selectively delivered as the microspheres permanently embed themselves within the tumor vascular bed. Use of SIRT has been conventionally aimed at treating primary hepatic tumors (hepatocellular carcinoma) or colorectal and neuroendocrine metastases. Numerous reviews are available for these tumor types. However, little is known or reviewed on non-colorectal or non-neuroendocrine primaries. Therefore, the aim of this paper is to systematically review the current literature to evaluate the effects of Yttrium-90 radioembolization on non-conventional liver tumors including those secondary to breast cancer, cholangiocarcinoma, ocular and percutaneous melanoma, pancreatic cancer, renal cell carcinoma, and lung cancer.     

The Effects of Hepatic Artery Chemotherapy on Viral Hepatitis in Patients With Hepatocellular Carcinoma

Transcatheter arterial chemoembolization (TACE) or arterial Yttrium-90 (⁹⁰Y) microspheres are used to treat unresectable hepatocellular carcinoma (HCC), but little is known about their effects on viral hepatitis. The aim of this study was to determine their effect on viral hepatitis in patients with HCC. We carried out a retrospective review of patients treated for HCC. Worsening of viral hepatitis was determined by serum chemistry and viral loads where available. Fifty-two patients treated with TACE were followed for a mean of 22.0 months. Thirty-nine patients (75%) had decreased/stable tumor. Two of the 39 (5%) patients with decreased/stable tumor burden had a sustained increase in bilirubin. None had a sustained ALT elevation or significant increase in viral load after TACE. Twenty-four patients treated with ⁹⁰Y microspheres were followed for a mean of 12.0 months. Twenty-two of these had a decreased/stable tumor burden and no patient had a significant elevation of ALT. However, 7 of the 22 had a sustained bilirubin elevation. We conclude that neither TACE nor ⁹⁰Y treatment was associated with worsening viral hepatitis in this group of HCC patients. The presence of chronic viral hepatitis with normal bilirubin should not exclude the use of these therapies in patients with unresectable HCC.     

Transarterial radioembolization for hepatocellular carcinoma: An update and perspectives

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.     

Radioembolization with yttrium-90 glass microspheres in hepatocellular carcinoma: European experience on safety and long-term survival

Radioembolization has been demonstrated to allow locoregional therapy of patients with hepatocellular carcinoma not eligible for transarterial chemoembolization or other local therapies. The aim of this study was to validate evidence of the safety and efficacy of this treatment in a European sample of patients with advanced hepatocellular carcinoma (HCC). Therefore, 108 consecutive patients with advanced HCC and liver cirrhosis were included. Yttrium-90 (Y-90) microspheres were administered in a lobar fashion over the right or left branch of the hepatic artery. The response to treatment was evaluated by computed tomography (CT) imaging applying Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization (WHO) criteria with recent European Association for the Study of the Liver / National Cancer Institute (EASL/NCI) amendments. Time to progression (TTP) and overall survival were estimated by the Kaplan-Meier method. In all, 159 treatment sessions were performed ranging between one to three treatments per patient. The mean radiation dose per treatment was 120 (± 18) Gy. According to EASL criteria, complete responses were determined in 3% of patients, partial responses in 37%, stable disease 53%, and primary progression in 6% of patients. TTP was 10.0 months, whereas the median overall survival was 16.4 months. No lung or visceral toxicity was observed. The most frequently observed adverse events was a transient fatigue-syndrome. CONCLUSION: Radioembolization with Y-90 glass microspheres for patients with advanced HCC is a safe and effective treatment which can be utilized even in patients with compromised liver function. Because TTP and survival appear to be comparable to systemic therapy in selected patients with advanced HCC, randomized controlled trials in combination with systemic therapy are warranted.     

钇90微球治疗原发性肝癌

本文讨论钇90微球治疗原发性肝细胞癌在临床上的应用。在适当选择和计划内放射剂量的情况下,钇90微球可以达到疗效高而副作用少的治疗目的。已发表的医学研究显示钇90微球可有效作为姑息性治疗T晚期肝癌,亦可作为肝移植前的肝癌过渡治疗,延长患者等候肝源的时间。钇90微球能把不能切除的肝癌降期到可切除,亦可把不能进行肝移植的肝癌变成为可以肝移植。使用钇90微球作为内放射肝段/肝叶切除的新方法的疗效非常理想。部分肝切除后肝癌复发的患者,钇90微球亦有理想的疗效。     

Transarterial chemoembolization versus transarterial radioembolization in hepatocellular carcinoma: optimization of selecting treatment modality

Hepatocellular carcinoma (HCC) of intermediate stage consists of diverse tumor and patient factors in terms of tumor number, size and liver function resulting in various outcomes given by transarterial chemoembolization (TACE). Transarterial radioembolization (TARE) using radioactive isotope, β-ray emitting Yttrium-90 with a short half-life and penetration depth, is an emerging intra-arterial brachytherapy characterized by potent anti-cancer effect given by radiation but minimal embolic effect. Although there is lack of study directly comparing the efficacy and safety between TACE and TARE in patients with unresectable HCC, several retrospective or small-scaled studies suggest that overall efficacy indicated by overall survival and time to progression is similar between two modalities and TARE has a superiority in the safety including postembolization syndrome, hospitalization days and outpatient-based therapy. In advanced HCC with portal vein (PV) invasion, TACE is not consistently recommended due to risk of hepatic decompensation or failure after procedure. On the contrary, available data suggest that TARE might be a promising treatment option in HCC with PV thrombosis if patient’s liver function is preserved and the level of PV invasion is less than main trunk. Ongoing trials comparing TARE and sorafenib in advanced HCC would elucidate the role of this locoregional therapy. The need of a multidisciplinary team, complex steps of procedure and high cost of TARE are the hurdles to widespread recommendation of this therapy in intermediate or advanced HCC. The optimization of selection between TACE and TARE might be dependent on availability, experience, tumor factors and patient factors.     

The optimal selection of radiotherapy treatment for hepatocellular carcinoma

The majority of patients who present with hepatocellular carcinoma (HCC) are already at an advanced stage, and the tumors are unresectable. Radiotherapy (RT) technology can safely provide focused high-dose irradiation to these patients. A wide spectrum of RT technologiesis currently available, including internal RT consisting of Yttrium-90 ((90)Y), Iodine-131 ((131)I) anti-ferritin antibody and Homium-199 ((199)Ho) and external RT, such as three-dimensional conformal RT, intensity-modulated RT, helical tomotherapy, stereotactic body RT, and image-guided RT. However, it may be difficult for physicians to understand all of the available options and to select the optimal RT treatment. Physicians frequently query radiation oncologists on the practical indications of RT for managing patients with HCC. According to the Korean Liver Cancer Study Group practice guidelines, RT is considered appropriate for unresectable, locally advanced HCC without extrahepatic metastasis, a Child-Pugh class A or B, and tumors that occupy less than two-thirds of the liver with level II evidence. In this review, we discuss the application of various RT modalities based on disease status and the detailed indications for RT according to the Barcelona Clinic Liver Cancer staging system.