Radiation Dose Limits and Liver Toxicities Resulting from Multiple Yttrium-90 Radioembolization Treatments for Hepatocellular Carcinoma

Young, Jeremy C.; Rhee, Thomas K.; Atassi, Bassel; Gates, Vanessa L.; Kulik, Laura; Mulcahy, Mary F.; Larson, Andrew C.; Ryu, Robert K.; Sato, Kent T.; Lewandowski, Robert J.; Omary, Reed A.; Salem, Riad

doi:10.1016/j.jvir.2007.07.016

Cited by 107 publications

(66 citation statements)

References 36 publications

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“…Liver toxicity is encountered with an overall low incidence (6)(7)(8)(9). Known risk factors are previous intraarterial therapy, chemotherapy, and high applied activities per target volume (7,9,10).…”

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confidence: 99%

⁹⁰Y Radioembolization After Radiation Exposure from Peptide Receptor Radionuclide Therapy

et al. 2012

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Previous radiation therapy of the liver is a contraindication for performing 90 Y microsphere radioembolization, and its safety after internal radiation exposure through peptide receptor radionuclide therapy (PRRT) has not yet been investigated. Methods: We retrospectively assessed a consecutive cohort of 23 neuroendocrine tumor (NET) patients with liver-dominant metastatic disease undergoing radioembolization with 90 Y microspheres as a salvage therapy after failed PRRT. Toxicity was recorded throughout follow-up and reported according to Common Terminology Criteria for Adverse Events (version 3). Radiologic (response evaluation criteria in solid tumors), biochemical, and symptomatic responses were investigated at 3 mo after treatment, and survival analyses were performed with the Kaplan-Meier method (log-rank test, P , 0.05). Results: The median follow-up period after radioembolization was 38 mo (95% confidence interval, 18-58 mo). The mean previous cumulative activity of 177 Lu-DOTA-octreotate was 31.8 GBq. The mean cumulative treatment activity of 90 Y microspheres was 3.4 6 2.1 GBq, administered to the whole liver in a single session (n 5 8 patients), in a sequential lobar fashion (n 5 10 patients), or to only 1 liver lobe (n 5 5 patients). Only transient, mostly minor liver toxicity (no grade 4) was recorded. One patient (4.3%) developed a gastroduodenal ulcer (grade 2). The overall response rates for radiologic, biochemical, and symptomatic responses were 30.4%, 53.8%, and 80%, respectively. The median overall survival was 29 mo (95% confidence interval, 4-54 mo) from the first radioembolization session and 54 mo (95% confidence interval, 47-61 mo) from the first PRRT cycle. A tumor proliferation index Ki-67 greater than 5% predicted shorter survival (P 5 0.007). Conclusion: Radioembolization is a safe and effective salvage treatment option in advanced NET patients with liverdominant tumor burden who failed or reprogressed after PRRT. The lack of relevant liver toxicity despite high applied 90 Y activities and considerable previous cumulative activities of 177 Lu-octreotate is noteworthy and disputes internal radiation exposure by PRRT as a toxicity risk factor in subsequent radioembolization.

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⁹⁰Y Radioembolization After Radiation Exposure from Peptide Receptor Radionuclide Therapy

et al. 2012

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“…The risk of RILD or liver failure, may be increased in patients who have low tumor/normal liver ratio following radiation delivery [75]. Radiation-induced lung injury has been shown to develop in more than 50% of cases with significant hepatopulmonary shunts [72].…”

Section: Sirtmentioning

confidence: 99%

Consensus for Radiotherapy in Hepatocellular Carcinoma from The 5th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2014): Current Practice and Future Clinical Trials

Park

Cheng

et al. 2016

Liver Cancer

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A consensus meeting to develop practice guidelines and to recommend future clinical trials for radiation therapy (RT), including external beam RT (EBRT), and selective internal RT (SIRT) in hepatocellular carcinoma (HCC) was held at the 5th annual meeting of the Asia-Pacific Primary Liver Cancer Expert consortium. Although there is no randomized phase III trial evidence, the efficacy and safety of RT in HCC has been shown by prospective and retrospective studies using modern RT techniques. Based on these results, the committee came to a consensus on the utility and efficacy of RT in the management of HCC according to each disease stage as follows: in early and intermediate stage HCC, if standard treatment is not compatible, RT, including EBRT and SIRT can be considered. In locally advanced stage HCC, combined EBRT with transarterial chemoembolization or hepatic arterial infusion chemotherapy, and SIRT can be considered. In terminal stage HCC, EBRT can be considered for palliation of symptoms and reduction of morbidity caused by the primary tumor or its metastases. Despite the currently reported benefits of RT in HCC, the committee agreed that there is a compelling need for large prospective studies, including randomized phase III trial evidence evaluating the role of RT. Specifically studies evaluating the efficacy and safety of sequential combination of EBRT and SIRT are strongly recommended.

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“…Due the hypervascularity of HCCs, radioactive microspheres theoretically flow preferentially by a factor of 3 to 1 [35] to tumors rather than hepatic parenchyma, limiting toxicity. Nonetheless, postembolization syndrome following TARE with nausea, abdominal pain and anorexia with or without fever occurs with roughly the same frequency as with TACE, though severity may be Byrne TJ et al .…”

Section: Radioembolizationmentioning

confidence: 99%

Loco-regional therapies for patients with hepatocellular carcinoma awaiting liver transplantation: Selecting an optimal therapy

Byrne

Rakela

2016

WJT

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Hepatocellular carcinoma (HCC) is a common, increasingly prevalent malignancy. For all but the smallest lesions, surgical removal of cancer via resection or liver transplantation (LT) is considered the most feasible pathway to cure. Resection -even with favorable survival -is associated with a fairly high rate of recurrence, perhaps since most HCCs occur in the setting of cirrhosis. LT offers the advantage of removing not only the cancer but the diseased liver from which the cancer has arisen, and LT outperforms resection for survival with selected patients. Since time waiting for LT is time during which HCC can progress, locoregional therapy (LRT) is widely employed by transplant centers. The purpose of LRT is either to bridge patients to LT by preventing progression and waitlist dropout, or to downstage patients who slightly exceed standard eligibility criteria initially but can fall within it after treatment. Transarterial chemoembolization and radiofrequency ablation have been the most widely utilized LRTs to date, with favorable efficacy and safety as a bridge to LT (and for the former, as a downstaging modality). The list of potentially effective LRTs has expanded in recent years, and includes transarterial chemoembolization with drug-eluting beads, radioembolization and novel forms of extracorporal therapy. Herein we appraise the various LRT modalities for HCC, and their potential roles in specific clinical scenarios in patients awaiting LT.

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Radiation Dose Limits and Liver Toxicities Resulting from Multiple Yttrium-90 Radioembolization Treatments for Hepatocellular Carcinoma

Cited by 107 publications

References 36 publications

⁹⁰Y Radioembolization After Radiation Exposure from Peptide Receptor Radionuclide Therapy

⁹⁰Y Radioembolization After Radiation Exposure from Peptide Receptor Radionuclide Therapy

Consensus for Radiotherapy in Hepatocellular Carcinoma from The 5th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2014): Current Practice and Future Clinical Trials

Loco-regional therapies for patients with hepatocellular carcinoma awaiting liver transplantation: Selecting an optimal therapy

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Radiation Dose Limits and Liver Toxicities Resulting from Multiple Yttrium-90 Radioembolization Treatments for Hepatocellular Carcinoma

Cited by 107 publications

References 36 publications

90Y Radioembolization After Radiation Exposure from Peptide Receptor Radionuclide Therapy

90Y Radioembolization After Radiation Exposure from Peptide Receptor Radionuclide Therapy

Consensus for Radiotherapy in Hepatocellular Carcinoma from The 5th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2014): Current Practice and Future Clinical Trials

Loco-regional therapies for patients with hepatocellular carcinoma awaiting liver transplantation: Selecting an optimal therapy

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⁹⁰Y Radioembolization After Radiation Exposure from Peptide Receptor Radionuclide Therapy

⁹⁰Y Radioembolization After Radiation Exposure from Peptide Receptor Radionuclide Therapy