Fibrosis, Portal Hypertension, and Hepatic Volume Changes Induced by Intra-arterial Radiotherapy with 90Yttrium Microspheres

Jakobs, Tobias; Saleem, Sheena; Atassi, Bassel; Reda, Edward F.; Lewandowski, Robert J.; Yaghmai, Vahid; Miller, Frank H.; Ryu, Robert K.; Ibrahim, Saad M.; Sato, Kent T.; Kulik, Laura; Mulcahy, Mary F.; Omary, Reed A.; Murthy, Ravi; Reiser, Maximilian; Salem, Riad

doi:10.1007/s10620-007-0148-z

Cited by 132 publications

(74 citation statements)

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“…Three patients (4%) presented with cirrhosis-like changes in the liver parenchyma, associated with severe symptoms of portal hypertension, including refractory ascites (n ¼ 2) and variceal upper gastrointestinal bleeding (n ¼ 1), respectively, 19, 12 and 12 months after 90 Y treatment. This complication, which we defined as REIPH, is most probably an extreme clinical presentation of the radiation-induced liver fibrosis described by Jacobs et al [11]. Potentially, this late complication might be avoided if these patients had received corticosteroids as suggested by Sangro et al [18].…”

Section: Discussionmentioning

confidence: 89%

“…Several observational cohort studies [4][5][6][7][8][9][10] as well as a few meta-analyses dealing with radioembolization for chemorefractory mCRC have been published, all of them demonstrating the relative safety of the radioembolization technique and the potential for better survival. However, only limited data on late toxicity of 90 Y in this patient population are available [11][12][13]. Additionally, little information is available about potential prognostic factors for prolonged survival.…”

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confidence: 99%

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Yttrium-90 radioembolization for the treatment of chemorefractory colorectal liver metastases: Technical results, clinical outcome and factors potentially influencing survival

et al. 2015

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90 Y radioembolization to treat chemorefractory colorectal liver metastases were identified. Demographic, laboratory, imaging and dosimetry data were collected. Post-treatment technical and clinical outcomes were analyzed as well as overall survival; finally several factors potentially influencing survival were analyzed. Results: In total 88 patients were selected for angiographic workup; 71 patients (81%) finally underwent catheter-directed 90 Y microsphere infusion into the hepatic artery 25 days (standard deviation 13 days) after angiographic workup. Median infused activity was 1809 MBq; 30-day toxicity included: fatigue (n ¼ 39; 55%), abdominal discomfort (n ¼ 33; 47%), nausea (n ¼ 5; 7%), fever (n ¼ 14; 20%), diarrhea (n ¼ 6; 9%), liver function abnormalities and elevated bilirubin (transient) (n ¼ 3; 4%). Gastric ulcer was found in five patients (7%). A late complication was radioembolization-induced portal hypertension (REIPH) in three patients (4%). Median time to progression in the liver was 4.4 months. Estimated survival at six and 12 months was 65% and 30%, respectively, with a 50% estimated survival after 8.0 months in this group of chemorefractory patients. Prognostic factors for worse survival were high preprocedural bilirubin, alkaline phosphatase and tumor volume levels. Conclusion:90 Y microsphere radioembolization for chemorefractory colorectal liver metastases has an acceptable safety profile with a 50% estimated survival after 8.0 months. Pretreatment high bilirubin, alkaline phosphatase and tumor volume levels were associated with early death.

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Section: Discussionmentioning

confidence: 89%

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confidence: 99%

Yttrium-90 radioembolization for the treatment of chemorefractory colorectal liver metastases: Technical results, clinical outcome and factors potentially influencing survival

et al. 2015

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“…The 4 patients who underwent no 99m Tc-MAA PVT targeting exhibited severe acute liver toxicity leading to death. One explanation is that radioembolization induces transient portal hypertension (19), which can be poorly tolerated by PVT patients who present with poor liver function and no accurate treatment of PVT because of the absence of targeting. The median OS was only 3 mo (95% CI, 3-3.7 mo) for patients with poor PVT targeting, compared with 20.2 mo (95% CI, 12-25.1 mo) for those with good PVT targeting (P , 0.0001).…”

Section: Discussionmentioning

confidence: 99%

Personalized Dosimetry with Intensification Using ⁹⁰Y-Loaded Glass Microsphere Radioembolization Induces Prolonged Overall Survival in Hepatocellular Carcinoma Patients with Portal Vein Thrombosis

Garin¹,

Rolland²,

Edeline³

et al. 2015

J Nucl Med

123

102

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The objective of this study was to evaluate the response rate and survival of hepatocellular carcinoma portal vein thrombosis (PVT) patients treated with 90 Y-loaded glass microspheres using a personalized dosimetry and intensification concept. Methods: The microspheres were administered to 41 hepatocellular carcinoma PVT patients (main 5 12; lobar/segmental 5 29). 99m Tc-macroaggregated albumin SPECT/CT quantitative analysis was used to calculate the tumor dose (TD), healthy injected liver dose (HILD), and injected liver dose (ILD). Response was evaluated at 3 mo using the criteria of the European Association for the Study of the Liver, with CT follow-up lasting until disease progression or death. Survival was assessed using the Kaplan-Meier method. Results: The mean injected activity was 3.1 ± 1.5 GBq, and mean ILD was 143 ± 49 Gy. When a TD threshold of 205 Gy was applied, 99m Tc-macroaggregated albumin SPECT/CT achieved a 100% sensitivity and 90% overall accuracy (0 false-negatives; 4 false-positives) in response prediction. On the basis of TD and HILD values, 37% of patients received an intensification of the treatment (increased injected activity with the aim of achieving a TD $ 205 Gy and HILD , 120 Gy, applying an ILD . 150 Gy). This intensification resulted in a high response rate (85%) without increased liver toxicity of grade 3 or higher (6% vs. 12% in the patients who did not receive treatment intensification; not statistically significant). For the total 41 patients, median overall survival (OS) was 18 mo (95% confidence interval, 11-25 mo). For patients with a TD of less than 205 Gy, median OS was 4.3 mo (3.7-5 mo), versus 18.2 mo (8.5-28.7 mo) for those with a TD of 205 Gy or more (P 5 0.005). Median OS was 20.9 mo for patients with a TD of 205 Gy or more and good PVT targeting (n 5 36). OS was 12 mo (3 mo to N) for patients with main PVT, versus 21.5 mo (12-28.7 mo) for those with segmental or lobar PVT (not statistically significant). For the 5 patients with complete portal vein revascularization who underwent lobar hepatectomy, median OS was not reached yet exceeded 24.5 mo and was significantly higher than that of other patients (P 5 0.0493). Conclusion: Using a 99m Tc-macroaggregated albumin SPECT/CT personalized dosimetry and intensification concept with 90 Y-loaded glass microspheres induced prolonged OS for PVT patients as compared with the standard of care (sorafenib), without increasing liver toxicity. Prospective randomized studies are therefore warranted.

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“…20 Nine studies, published between 2008 and 2014 were identified. [11][12][13][14][15][16][17][18][19] Three studies 11,12,15 were reported from the same centre with overlapping patient cohorts. Two studies 11,12 were excluded; and only the most recent (and largest) report 15 was included.…”

Section: Data Extractionmentioning

confidence: 99%

A systematic review of contralateral liver lobe hypertrophy after unilobar selective internal radiation therapy with Y90

Teo

Allen

et al. 2015

HPB

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Fibrosis, Portal Hypertension, and Hepatic Volume Changes Induced by Intra-arterial Radiotherapy with 90Yttrium Microspheres

Abstract: (90)Yttrium radioembolization utilizing glass microspheres in patients with liver metastases results in changes of hepatic parenchymal volume and also induced findings suggestive of fibrosis and portal hypertension. Further studies assessing the long-term effects are warranted.

Cited by 132 publications

References 47 publications

Yttrium-90 radioembolization for the treatment of chemorefractory colorectal liver metastases: Technical results, clinical outcome and factors potentially influencing survival

Yttrium-90 radioembolization for the treatment of chemorefractory colorectal liver metastases: Technical results, clinical outcome and factors potentially influencing survival

Personalized Dosimetry with Intensification Using ⁹⁰Y-Loaded Glass Microsphere Radioembolization Induces Prolonged Overall Survival in Hepatocellular Carcinoma Patients with Portal Vein Thrombosis

A systematic review of contralateral liver lobe hypertrophy after unilobar selective internal radiation therapy with Y90

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Fibrosis, Portal Hypertension, and Hepatic Volume Changes Induced by Intra-arterial Radiotherapy with 90Yttrium Microspheres

Abstract: (90)Yttrium radioembolization utilizing glass microspheres in patients with liver metastases results in changes of hepatic parenchymal volume and also induced findings suggestive of fibrosis and portal hypertension. Further studies assessing the long-term effects are warranted.

Cited by 132 publications

References 47 publications

Yttrium-90 radioembolization for the treatment of chemorefractory colorectal liver metastases: Technical results, clinical outcome and factors potentially influencing survival

Yttrium-90 radioembolization for the treatment of chemorefractory colorectal liver metastases: Technical results, clinical outcome and factors potentially influencing survival

Personalized Dosimetry with Intensification Using 90Y-Loaded Glass Microsphere Radioembolization Induces Prolonged Overall Survival in Hepatocellular Carcinoma Patients with Portal Vein Thrombosis

A systematic review of contralateral liver lobe hypertrophy after unilobar selective internal radiation therapy with Y90

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Personalized Dosimetry with Intensification Using ⁹⁰Y-Loaded Glass Microsphere Radioembolization Induces Prolonged Overall Survival in Hepatocellular Carcinoma Patients with Portal Vein Thrombosis