Description
Policy Application
DOS (Date of Service): All claims submitted for this policy will be processed accordingly to the policy effective date and associated revision effective dates in effect on the date of service.
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Treatments for Hepatic and Neuroendocrine Tumors
The use of external-beam radiotherapy and the application of more advanced radiotherapy approaches (e.g., intensity-modulated radiotherapy) may be of limited use in individuals with multiple diffuse lesions due to the low tolerance of the normal liver to radiation compared with the higher doses of radiation needed to kill the tumor.
Radioembolization
Radioembolization (referred to as selective internal radiotherapy in older literature) delivers small beads (microspheres) impregnated with yttrium-90 (Y90) intra-arterially via the hepatic artery. The microspheres, which become permanently embedded, are delivered to tumors preferentially because the hepatic circulation is uniquely organized, whereby tumors greater than 0.5 cm rely on the hepatic artery for blood supply while the normal liver is primarily perfused via the portal vein. Y90 is a pure beta-emitter with a relatively limited effective range and a short half-life that helps focus the radiation and minimize its spread.
Summary of Evidence
For individuals who have unresectable hepatocellular carcinoma who receive RE or RE with a liver transplant, the evidence includes primarily retrospective and prospective nonrandomized studies, with limited evidence from randomized controlled trials (RCTs). Relevant outcomes are overall survival (OS), functional outcomes, quality of life, and treatment-related morbidity. Nonrandomized studies have suggested that RE has high response rates compared with historical controls. Two (2) small pilot RCTs have compared RE with alternative therapies for hepatocellular carcinoma, including transarterial chemoembolization and transarterial chemoembolization with drug-eluting beads. Both trials reported similar outcomes for RE compared with alternatives. Evidence from nonrandomized studies has demonstrated that RE can permit successful liver transplantation in certain individuals. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.
For individuals who have unresectable intrahepatic cholangiocarcinoma who receive RE, the evidence includes a phase two (2) study and case series. Relevant outcomes are OS, functional outcomes, quality of life, and treatment-related morbidity. Comparisons of these case series to case series of alternative treatments have suggested that RE for primary intrahepatic cholangiocarcinoma has response rates similar to those seen with standard chemotherapy. Due to high study heterogeneity, it is difficult to identify individuals that are most likely to benefit from treatment. A phase two (2) study of RE with chemotherapy in the first-line setting reported a response rate of 39% and a disease control rate of 98%. The efficacy of RE in the neoadjuvant setting is being evaluated in an ongoing follow-up RCT. However, at this time, the evidence is not yet sufficiently robust to draw definitive conclusions about treatment efficacy. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.
For individuals who have unresectable neuroendocrine tumors who receive RE, the evidence includes an open-label phase two (2) study, retrospective reviews, and case series, some of which have compared RE with other transarterial liver-directed therapies. Relevant outcomes are OS, functional outcomes, quality of life, and treatment-related morbidity. This evidence has suggested that RE provides outcomes similar to standard therapies and historical controls for patients with neuroendocrine tumor-related symptoms or progression of the liver tumor. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.
For individuals who have unresectable intrahepatic metastases from colorectal cancer and prior treatment failure who receive RE, the evidence includes several small- to moderate-sized RCTs, prospective trials, and retrospective studies using a variety of comparators, as well as systematic reviews of these studies. Relevant outcomes are OS, functional outcomes, quality of life, and treatment-related morbidity. While studies of individuals with prior chemotherapy failure have methodologic problems and have not shown definitive superiority of RE compared with alternatives in terms of survival benefit, they tend to show greater tumor response and significantly delayed disease progression, particularly with combined use of RE and chemotherapy. For example, the EPOCH RCT found significantly prolonged primary endpoints of PFS (HR, 0.69; 95% CI, 0.54 to 0.88) and hepatic PFS (HR, 0.59; 95% CI, 0.46 to 0.77) with combined RE and chemotherapy in individuals who had progressed on first-line chemotherapy. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.
For individuals who have unresectable intrahepatic metastases from other cancers (e.g., breast, melanoma, pancreatic) who receive RE, the evidence includes nonrandomized studies. Relevant outcomes are OS, functional outcomes, quality of life, and treatment-related morbidity. These studies have shown significant tumor response; however, improvement in survival has not been demonstrated in controlled comparative studies. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.
