Abstract
Purpose: To investigate safety, response, and survival after ablative glass microsphere 90Y radioembolization for unresectable intrahepatic cholangiocarcinoma.Materials and Methods: A retrospective review of 37 radioembolizations in 28 patients treated with single compartment dose of ≥190 Gy encompassing >75% of the largest tumor was performed. Tumors were assessed for stage, morphology, and arterial supply. Response per Modified Response Evaluation Criteria in Solid Tumors (mRECIST), freedom from progression (FFP), progression-free survival (PFS), overall survival (OS), biochemical hepatic function, performance status, and adverse events were investigated.Results: The median highest dose per patient was 256.8 Gy (195.7–807.8). Objective response at 3 months was 94.1% (complete 44.1% and partial 50%). Median OS was not reached and the 30-month OS rate was 59%, with a median follow-up of 13.4 months (5.4–39.4). FFP in the radiated field and overall FFP at 30 months were 67% and 40%, respectively. Favorable arterial supply was associated with improved OS (p = 0.018). Unfavorable arterial supply was associated with worse OS [HR 5.7 (95% CI 1.1–28.9, p = 0.034)], and PFS [HR 5.9 (95% CI 1.9–18.4, p = 0.002)]. Patients with mass-forming tumors had a survival benefit (p = 0.002). Laboratory values and performance status did not significantly change 3 months after radioembolization. Grade 3 and 4 adverse events occurred in 2 (7.1%) patients.Conclusions: Radioembolization of unresectable intrahepatic cholangiocarcinoma with ablative intent has a high response rate, promising survival, and is well tolerated.
Highlights
Intrahepatic cholangiocarcinoma is the second most common primary hepatic malignancy following hepatocellular carcinoma (HCC) [1]
Unfavorable arterial supply was associated with worse overall survival (OS) [hazard ratio (HR) 5.7], and progression-free survival (PFS) [HR 5.9]
Following basic principles of radiation biology, this approach has led to improved outcomes when used for the treatment of hepatocellular carcinoma where Medical Internal Radiation Dose (MIRD) doses >190 Gy have resulted in increased tumor pathologic necrosis [7]
Summary
Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary hepatic malignancy following hepatocellular carcinoma (HCC) [1]. Palliative locoregional therapies are offered to select patients with unresectable iCCA and are recommended by the National Comprehensive Cancer Network guidelines [5]. Transarterial radioembolization using Yttrium-90containing microspheres for the treatment of HCC has advanced over the past two decades from a palliative intent treatment to an ablative modality applicable as first line definitive therapy in select patients. Administering high doses of radiation to expendable volumes of liver, known as radiation segmentectomy (two Couinaud segments or less) and lobectomy, has improved both the safety and efficacy of radioembolization. Radiopathologic www.oncotarget.com analyses have supported improved pathologic necrosis rates when ablative doses are prescribed, of which 190 Gray (Gy) has shown to represent a minimal efficacy threshold [6, 7]. Unresectable iCCA presents with blood supply variation and anatomic complexity, which may affect outcomes [8]
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