AIM: To further define variables associated with increased incidences of severe toxicities following administration of yttrium-90 (<sup>90</sup>Y) microspheres.METHODS: Fifty-eight patients undergoing 79 t...AIM: To further define variables associated with increased incidences of severe toxicities following administration of yttrium-90 (<sup>90</sup>Y) microspheres.METHODS: Fifty-eight patients undergoing 79 treatments were retrospectively assessed for development of clinical and laboratory toxicity incidence following <sup>90</sup>Y administration. Severe toxicity events were defined using Common Terminology Criteria for Adverse Events version 4.03 and defined as grade ≥ 3. Univariate logistic regression analyses were used to evaluate the effect of different factors on the incidence of severe toxicity events. Multicollinearity was assessed for all factors with P < 0.1 using Pearson correlation matrices. All factors not excluded due to multicollinearity were included in a multivariate logistic regression model for each measurement of severe toxicity.RESULTS: Severe (grade ≥ 3) toxicities occurred following 21.5% of the 79 treatments included in our analysis. The most common severe laboratory toxicities were severe alkaline phosphatase (17.7%), albumin (12.7%), and total bilirubin (10.1%) toxicities. Decreased pre-treatment albumin (OR = 26.2, P = 0.010) and increased pre-treatment international normalized ratio (INR) (OR = 17.7, P = 0.048) were associated with development of severe hepatic toxicity. Increased pre-treatment aspartate aminotransferase (AST; OR = 7.4, P = 0.025) and decreased pre-treatment hemoglobin (OR = 12.5, P = 0.025) were associated with severe albumin toxicity. Increasing pre-treatment model for end-stage liver disease (MELD) score (OR = 1.8, P = 0.033) was associated with severe total bilirubin toxicity. Colorectal adenocarcinoma histology was associated with severe alkaline phosphatase toxicity (OR = 5.4, P = 0.043).CONCLUSION: Clinicians should carefully consider pre-treatment albumin, INR, AST, hemoglobin, MELD, and colorectal histology when choosing appropriate candidates for <sup>90</sup>Y microsphere therapy.展开更多
Liver malignancy,including primary liver cancer and metastatic liver cancer has become one of the most common causes of cancer-related death worldwide due to the high malignant degree and limited systematic treatment ...Liver malignancy,including primary liver cancer and metastatic liver cancer has become one of the most common causes of cancer-related death worldwide due to the high malignant degree and limited systematic treatment strategy.Radioembolization with yttrium-90(^(90)Y)-loaded microspheres is a relatively novel technology that has made significant progress in the local treatment of liver malignancy.The different steps in the extensive work-up of radioembolization for patients with an indication for treatment with^(90)Y microspheres,from patient selection to follow up,both technically and clinically,are discussed in this paper.It describes the application and development of^(90)Y microspheres in the treatment of liver cancer.展开更多
Hepatocellular carcinoma (HCC) recurs with a reported frequency of 12%-18% after liver transplantation. Recurrence is associated with a mortality rate exceeding 75%. Approximately one-third of recurrences develop in...Hepatocellular carcinoma (HCC) recurs with a reported frequency of 12%-18% after liver transplantation. Recurrence is associated with a mortality rate exceeding 75%. Approximately one-third of recurrences develop in the transplanted liver and are therefore amenable to local therapy. A variety of treatment modalities have been reported including resection, transarterial chemoembolization (TACE), radiofrequency ablation (RFA), ethanol ablation, cryoablation, and external beam irradiation. Goals of treatment are tumor control and the minimization of toxic effect to functional parenchyma. Efficacy of treatment is mitigated by the need for ongoing immunosuppression. Yttrium-90 microspheres have been used as a treatment modality both for primary HCC and for pre-transplant management of HCC with promising results. Twenty-two months after liver transplantation for hepatitis C cirrhosis complicated by HCC, a 42-year old man developed recurrence of HCC in his transplant allograft. Treatment of multiple right lobe lesions with anatomic resection and adjuvant chemotherapy was unsuccessful. Multifocal recurrence in the remaining liver allograft was treated with hepatic intra-arterial infusion of yttrium-90 microspheres (SIR-Spheres, Sirtex Medical Inc., Lake Forest, IL, USA). Efficacy was demonstrated by tumor necrosis on imaging and a decrease in alpha-fetoprotein (AFP) level. There were no adverse consequences of initial treatment.展开更多
BACKGROUND Surgical resection and liver transplantation(LT)are the most effective curative options for hepatocellular carcinoma(HCC).However,few patients with huge HCC(>10 cm in diameter),especially those with port...BACKGROUND Surgical resection and liver transplantation(LT)are the most effective curative options for hepatocellular carcinoma(HCC).However,few patients with huge HCC(>10 cm in diameter),especially those with portal vein tumor thrombus(PVTT),can receive these treatments.Selective internal radiation therapy(SIRT)can be used as a conversion therapy for them because it has the dual benefit of shrinking tumors and increasing residual hepatic volume.However,in patients with huge HCC,high lung absorbed dose often prevents them from receiving SIRT.CASE SUMMARY A 35-year-old man was admitted because of emaciation and pain in the hepatic region for about 1 month.The computed tomography scan showed a 20.2 cm×19.8 cm tumor located in the right lobe–left medial lobes with right portal vein and right hepatic vein invasion.After the pathological type of HCC was confirmed by biopsy,two conversions were presented.The first one was drug-eluting bead transarterial chemoembolization plus hepatic arterial infusion chemotherapy and lenvatinib and sintilimab,converted to SIRT,and the second one was sequential SIRT with continued systemic treatment.The tumor size significantly decreased from 20.2 cm×19.8 cm to 16.2 cm×13.8 cm,then sequentially to 7.8 cm×6.8 cm.In the meantime,the ratio of spared volume to total liver volume increased gradually from 34.4%to 55.7%,then to 62.9%.Furthermore,there was visualization of the portal vein,indicating regression of the tumor thrombus.Finally,owing to the new tumor in the left lateral lobe,the patient underwent LT instead of resection without major complications.CONCLUSION Patients with inoperable huge HCC with PVTT could be converted to SIRT first and accept surgery sequentially.展开更多
Transarterial chemoembolization (TACE) is a form of intra-arterial catheter-based chemotherapy that selectively delivers high doses of cytotoxic drug to the tumor bed combining with the effect of ischemic necrosis i...Transarterial chemoembolization (TACE) is a form of intra-arterial catheter-based chemotherapy that selectively delivers high doses of cytotoxic drug to the tumor bed combining with the effect of ischemic necrosis induced by arterial embolization. Chemoembolization and radioembolization are at the core of the treatment of liver hepatocellular carcinoma (HCC) patients who cannot receive potentially curative therapies such as transplantation, resection or percutaneous ablation. TACE for liver cancer has been proven to be useful in local tumor control, to prevent tumor progression, prolong patients' life and control patient symptoms. Recent evidence showed in patients with single-nodule HCC of 3 cm or smaller without vascular invasion, the 5-year overall survival (OS) with TACE was similar to that with hepatic resection and radiofrequency ablation. Mthough being used for decades, Lipiodol~ (Lipiodol~ Ultra Fluid~, Guerbet, France) remains important as a tumor-seeking and radio-opaque clrug delivery vector in intervendonal oncology. There have been efforts to improve the delivery of chemotherapeutic agents to tumors. Drug-eluting bead (DEB) is a relatively novel drug delivery embolization system which allows for fixed dosing and the ability to release the anticancer agents in a sustained manner. Three DEBs are available, i.e., Tandem~ (CeloNova Biosciences Inc., USA), DC-Beads~ (BTG, UK) and HepaSphere~ (BioSphere Medical, Inc., USA). Transarterial radioembolization (TARE) technique has been developed, and proven to be efficient and safe in advanced liver cancers and those with vascular complications. Two types of radioembolization microspheres are available i.e., SIR-Spheres~ (Sirtex Medical Limited, Australia) and TheraSphere~ (BTG, UK). This review describes the basic procedure of TACE, properties and efficacy of some chemoembolization systems and radioembolization agents which are commercially available and/or currently under clinical evaluation. The key clinical trials of transcatheter arterial therapy for liver cancer are summarized.展开更多
基金Supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR00165 through our institution’s Center for Clinical and Translational Science(in part)
文摘AIM: To further define variables associated with increased incidences of severe toxicities following administration of yttrium-90 (<sup>90</sup>Y) microspheres.METHODS: Fifty-eight patients undergoing 79 treatments were retrospectively assessed for development of clinical and laboratory toxicity incidence following <sup>90</sup>Y administration. Severe toxicity events were defined using Common Terminology Criteria for Adverse Events version 4.03 and defined as grade ≥ 3. Univariate logistic regression analyses were used to evaluate the effect of different factors on the incidence of severe toxicity events. Multicollinearity was assessed for all factors with P < 0.1 using Pearson correlation matrices. All factors not excluded due to multicollinearity were included in a multivariate logistic regression model for each measurement of severe toxicity.RESULTS: Severe (grade ≥ 3) toxicities occurred following 21.5% of the 79 treatments included in our analysis. The most common severe laboratory toxicities were severe alkaline phosphatase (17.7%), albumin (12.7%), and total bilirubin (10.1%) toxicities. Decreased pre-treatment albumin (OR = 26.2, P = 0.010) and increased pre-treatment international normalized ratio (INR) (OR = 17.7, P = 0.048) were associated with development of severe hepatic toxicity. Increased pre-treatment aspartate aminotransferase (AST; OR = 7.4, P = 0.025) and decreased pre-treatment hemoglobin (OR = 12.5, P = 0.025) were associated with severe albumin toxicity. Increasing pre-treatment model for end-stage liver disease (MELD) score (OR = 1.8, P = 0.033) was associated with severe total bilirubin toxicity. Colorectal adenocarcinoma histology was associated with severe alkaline phosphatase toxicity (OR = 5.4, P = 0.043).CONCLUSION: Clinicians should carefully consider pre-treatment albumin, INR, AST, hemoglobin, MELD, and colorectal histology when choosing appropriate candidates for <sup>90</sup>Y microsphere therapy.
文摘Liver malignancy,including primary liver cancer and metastatic liver cancer has become one of the most common causes of cancer-related death worldwide due to the high malignant degree and limited systematic treatment strategy.Radioembolization with yttrium-90(^(90)Y)-loaded microspheres is a relatively novel technology that has made significant progress in the local treatment of liver malignancy.The different steps in the extensive work-up of radioembolization for patients with an indication for treatment with^(90)Y microspheres,from patient selection to follow up,both technically and clinically,are discussed in this paper.It describes the application and development of^(90)Y microspheres in the treatment of liver cancer.
文摘Hepatocellular carcinoma (HCC) recurs with a reported frequency of 12%-18% after liver transplantation. Recurrence is associated with a mortality rate exceeding 75%. Approximately one-third of recurrences develop in the transplanted liver and are therefore amenable to local therapy. A variety of treatment modalities have been reported including resection, transarterial chemoembolization (TACE), radiofrequency ablation (RFA), ethanol ablation, cryoablation, and external beam irradiation. Goals of treatment are tumor control and the minimization of toxic effect to functional parenchyma. Efficacy of treatment is mitigated by the need for ongoing immunosuppression. Yttrium-90 microspheres have been used as a treatment modality both for primary HCC and for pre-transplant management of HCC with promising results. Twenty-two months after liver transplantation for hepatitis C cirrhosis complicated by HCC, a 42-year old man developed recurrence of HCC in his transplant allograft. Treatment of multiple right lobe lesions with anatomic resection and adjuvant chemotherapy was unsuccessful. Multifocal recurrence in the remaining liver allograft was treated with hepatic intra-arterial infusion of yttrium-90 microspheres (SIR-Spheres, Sirtex Medical Inc., Lake Forest, IL, USA). Efficacy was demonstrated by tumor necrosis on imaging and a decrease in alpha-fetoprotein (AFP) level. There were no adverse consequences of initial treatment.
文摘BACKGROUND Surgical resection and liver transplantation(LT)are the most effective curative options for hepatocellular carcinoma(HCC).However,few patients with huge HCC(>10 cm in diameter),especially those with portal vein tumor thrombus(PVTT),can receive these treatments.Selective internal radiation therapy(SIRT)can be used as a conversion therapy for them because it has the dual benefit of shrinking tumors and increasing residual hepatic volume.However,in patients with huge HCC,high lung absorbed dose often prevents them from receiving SIRT.CASE SUMMARY A 35-year-old man was admitted because of emaciation and pain in the hepatic region for about 1 month.The computed tomography scan showed a 20.2 cm×19.8 cm tumor located in the right lobe–left medial lobes with right portal vein and right hepatic vein invasion.After the pathological type of HCC was confirmed by biopsy,two conversions were presented.The first one was drug-eluting bead transarterial chemoembolization plus hepatic arterial infusion chemotherapy and lenvatinib and sintilimab,converted to SIRT,and the second one was sequential SIRT with continued systemic treatment.The tumor size significantly decreased from 20.2 cm×19.8 cm to 16.2 cm×13.8 cm,then sequentially to 7.8 cm×6.8 cm.In the meantime,the ratio of spared volume to total liver volume increased gradually from 34.4%to 55.7%,then to 62.9%.Furthermore,there was visualization of the portal vein,indicating regression of the tumor thrombus.Finally,owing to the new tumor in the left lateral lobe,the patient underwent LT instead of resection without major complications.CONCLUSION Patients with inoperable huge HCC with PVTT could be converted to SIRT first and accept surgery sequentially.
文摘Transarterial chemoembolization (TACE) is a form of intra-arterial catheter-based chemotherapy that selectively delivers high doses of cytotoxic drug to the tumor bed combining with the effect of ischemic necrosis induced by arterial embolization. Chemoembolization and radioembolization are at the core of the treatment of liver hepatocellular carcinoma (HCC) patients who cannot receive potentially curative therapies such as transplantation, resection or percutaneous ablation. TACE for liver cancer has been proven to be useful in local tumor control, to prevent tumor progression, prolong patients' life and control patient symptoms. Recent evidence showed in patients with single-nodule HCC of 3 cm or smaller without vascular invasion, the 5-year overall survival (OS) with TACE was similar to that with hepatic resection and radiofrequency ablation. Mthough being used for decades, Lipiodol~ (Lipiodol~ Ultra Fluid~, Guerbet, France) remains important as a tumor-seeking and radio-opaque clrug delivery vector in intervendonal oncology. There have been efforts to improve the delivery of chemotherapeutic agents to tumors. Drug-eluting bead (DEB) is a relatively novel drug delivery embolization system which allows for fixed dosing and the ability to release the anticancer agents in a sustained manner. Three DEBs are available, i.e., Tandem~ (CeloNova Biosciences Inc., USA), DC-Beads~ (BTG, UK) and HepaSphere~ (BioSphere Medical, Inc., USA). Transarterial radioembolization (TARE) technique has been developed, and proven to be efficient and safe in advanced liver cancers and those with vascular complications. Two types of radioembolization microspheres are available i.e., SIR-Spheres~ (Sirtex Medical Limited, Australia) and TheraSphere~ (BTG, UK). This review describes the basic procedure of TACE, properties and efficacy of some chemoembolization systems and radioembolization agents which are commercially available and/or currently under clinical evaluation. The key clinical trials of transcatheter arterial therapy for liver cancer are summarized.