Abstract
Simple SummaryRadioembolization has failed to prove survival benefit in randomized trials, and, depending on various factors including tumor biology, response rates may vary considerably. Studies showed positive correlations between survival and absorbed tumor dose. Therefore, increasing currently prescribed tumor doses may be favorable for improving patient outcomes. The dominant limiting factor for increasing RE dose prescriptions is the relatively low tolerance of liver parenchyma to radiation with the possible consequence of a radiation-induced liver disease. Advances in RILD prevention may help increasing tolerable radiation doses to improve patient outcomes. Our study aimed to evaluate the impact of post-therapeutic RILD-prophylaxis in a cohort of intensely pretreated liver metastatic breast cancer patients. The results of this study as well as pathophysiological considerations warrant further investigations of RILD prophylaxis to increase dose prescriptions in radioembolization.Background: Radioembolization (RE) with yttrium-90 (90Y) resin microspheres yields heterogeneous response rates in with primary or secondary liver cancer. Radiation-induced liver disease (RILD) is a potentially life-threatening complication with higher prevalence in cirrhotics or patients exposed to previous chemotherapies. Advances in RILD prevention may help increasing tolerable radiation doses to improve patient outcomes. This study aimed to evaluate the impact of post-therapeutic RILD-prophylaxis in a cohort of intensely pretreated liver metastatic breast cancer patients; Methods: Ninety-three patients with liver metastases of breast cancer received RE between 2007 and 2016. All Patients received RILD prophylaxis for 8 weeks post-RE. From January 2014, RILD prophylaxis was changed from ursodeoxycholic acid (UDCA) and prednisolone (standard prophylaxis [SP]; n = 59) to pentoxifylline (PTX), UDCA and low-dose low molecular weight heparin (LMWH) (modified prophylaxis (MP); n = 34). The primary endpoint was toxicity including symptoms of RILD; Results: Dose exposure of normal liver parenchyma was higher in the modified vs. standard prophylaxis group (47.2 Gy (17.8–86.8) vs. 40.2 Gy (12.5–83.5), p = 0.017). All grade RILD events (mild: bilirubin ≥ 21 µmol/L (but <30 μmol/L); severe: (bilirubin ≥ 30 µmol/L and ascites)) were observed more frequently in the SP group than in the MP group, albeit without significance (7/59 vs. 1/34; p = 0.140). Severe RILD occurred in the SP group only (n = 2; p > 0.1). ALBI grade increased in 16.7% patients in the MP and in 27.1% patients in the SP group, respectively (group difference not significant); Conclusions: At established dose levels, mild or severe RILD events proved rare in our cohort. RILD prophylaxis with PTX, UDCA and LMWH appears to have an independent positive impact on OS in patients with metastatic breast cancer and may reduce the frequency and severity of RILD. Results of this study as well as pathophysiological considerations warrant further investigations of RILD prophylaxis presumably targeting combinations of anticoagulation (MP) and antiinflammation (SP) to increase dose prescriptions in radioembolization.
Highlights
Radioembolization with yttrium-90 (90Y)-loaded resin microspheres (RE, or selective internal radiation therapy [SIRT]) has emerged as an alternative treatment option for patients with primary and secondary liver cancer
Grade increased in 16.7% patients in the modified prophylaxis (MP) and in 27.1% patients in the SP group, respectively; Conclusions: At established dose levels, mild or severe Radiation-induced liver disease (RILD) events proved rare in our cohort
Of the nine patients with planned sequential therapy who discontinued treatment after the first session, treatment of the contralateral lobe was cancelled in three patients due to confluent lobar liver injury after ipsilateral RE, depicted by decreased Gd-EOB-DTPA uptake in magnetic resonance imaging (MRI) before the second treatment session
Summary
Radioembolization with yttrium-90 (90Y)-loaded resin microspheres (RE, or selective internal radiation therapy [SIRT]) has emerged as an alternative treatment option for patients with primary and secondary liver cancer. Dominant limiting factor for increasing RE dose prescriptions is the relatively low tolerance of liver parenchyma to radiation, which can lead to a deterioration in liver function and even hepatic failure, typically 2 weeks to 4 months after RE [12]. This syndrome is known as radioembolization- or radiation-induced liver disease (RILD). A prospective study demonstrated significant mitigation of early focal radiation induced liver injury (fRILI) by post-therapeutic administration of pentoxifylline (PTX), ursodeoxycholic acid (UDCA) and low-molecular weight heparin (LMWH) in patients who underwent imageguided high-dose-rate interstitial brachytherapy of liver metastases [20]. Results of this study as well as pathophysiological considerations warrant further investigations of RILD prophylaxis presumably targeting combinations of anticoagulation (MP) and antiinflammation (SP) to increase dose prescriptions in radioembolization
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