Survival Outcomes of a Salvage Patient Population after Radioembolization of Hepatic Metastases with Yttrium-90 Microspheres

Evans, Kathryn A.; Richardson, Matthew; Pavlakis, Nick; Morris, David L.; Liauw, Winston; Bester, Lourens

doi:10.1016/j.jvir.2010.06.018

Cited by 31 publications

(13 citation statements)

References 34 publications

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“…SIRT delivers beta-emitting yttrium-90 ( 90 Y) microspheres to liver tumors through the hepatic arterial system and is able to largely spare the normal liver because of the short distance over which radiation is emitted from each microsphere. SIRT has been studied as first-line therapy for hepatic colorectal metastases (7)(8)(9)(10), in combination with secondor third-line chemotherapy (11,12), and as salvage therapy for chemorefractory patients (13)(14)(15)(16)(17)(18). These studies have been important in demonstrating that SIRT can prolong intrahepatic disease control and improve OS.…”

Section: Introductionmentioning

confidence: 99%

Pretreatment tumor volume as a prognostic factor in metastatic colorectal cancer treated with selective internal radiation to the liver using yttrium-90 resin microspheres

Bhooshan

Sharma

Badiyan³

et al. 2016

J. Gastrointest. Oncol.

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Background: Yttrium-90 ( 90 Y)-resin microspheres can prolong intrahepatic disease control and improve overall survival (OS) in patients with metastatic colorectal cancer (CRC). Prognostic factors for improved outcomes in patients undergoing selective internal radiation therapy (SIRT) have been studied, but the relationship between pre-SIRT liver tumor volume and outcomes has not well described. Methods: We retrospectively reviewed the records of patients with metastatic CRC who were treated at our institution with 90 Y-resin microspheres. Each patient underwent either MR or CT imaging of the liver with intravenous (IV) contrast before and within ~2-3 months after SIRT. Imaging data were transferred into our treatment planning system. Each metastatic liver lesion was contoured, and the volume of each lesion was summed to determine the total liver tumor volume at a given time point. We evaluated whether pretreatment liver tumor volume was related to OS. We also evaluated the relationship between pre-SIRT tumor volume and radiographic treatment response by either unidimensional Response Evaluation Criteria in Solid Tumors (RECIST) or three-dimensional volumetric criteria. Results: We included 60 patients with a median age of 59 years (range, 38-97 years); 60% of patients received sequential lobar treatment. The median number of chemotherapy cycles received prior to SIRT was 2. Median follow-up from first SIRT was 8.9 months. Pre-and post-SIRT tumor volumes were primarily calculated on CT (87%). The median pre-SIRT tumor volume was 77 cc (range, 4.5-2,170.4 cc). The median intervals between the first SIRT and the first, second, and third follow-up scans were 2.2, 4.4, and 7.7 months, respectively. No patient experienced a radiographic complete response. Pretreatment volume was a significant predictor for estimating the odds of a patient having stable disease or partial response using volumetric response criteria at first (P=0.016), second (P=0.023), and third (P=0.015) follow-ups. For each unit increase in log volume, a patient's odds of having a stable or partial response were 0.57, 0.63, and 0.61 times as likely at first, second, and third follow-up, respectively. OS was not significantly associated with pretreatment tumor volume. Conclusions: Patients with metastatic CRC with larger overall pretreatment liver tumor volumes, regardless of number of individual liver lesions, are less likely to have radiographic evidence of stable disease or partial response following SIRT using volumetric response criteria. However, pretreatment volume was not significantly associated with OS, and thus SIRT should be considered for patients with larger pretreatment volumetric tumor burden.

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Section: Introductionmentioning

confidence: 99%

Pretreatment tumor volume as a prognostic factor in metastatic colorectal cancer treated with selective internal radiation to the liver using yttrium-90 resin microspheres

Bhooshan

Sharma

Badiyan³

et al. 2016

J. Gastrointest. Oncol.

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“…The β-emitter 90 Y is used for an increasing number of therapeutic radiopharmaceuticals, including the CD20 antibody ibritumomab tiuxetan, the somatostatin receptor ligands DOTATOC and DOTATATE, and microspheres for treatment of liver metastases (1–3). Because of its high β energy (Emax, 2.28 MeV), 90 Y can deliver therapeutically effective radiation doses at relatively low activity concentrations.…”

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confidence: 99%

Cerenkov Luminescence Imaging for Radiation Dose Calculation of a ⁹⁰Y-Labeled Gastrin-Releasing Peptide Receptor Antagonist

et al. 2015

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90Y has been used to label various new therapeutic radiopharmaceuticals. However, measuring the radiation dose delivered by 90Y is challenging because of the absence of suitable γ emissions and its low abundance of positron emissions. For the treatment of prostate cancer, radiolabeled gastrin-releasing peptide receptor (GRPr) antagonists have yielded promising results in mouse models. In this study, we evaluated whether Cerenkov luminescence imaging (CLI) could be used to determine radiation doses of a 90Y-labeled GRPr antagonist in nude mice. Methods Mice bearing subcutaneous prostate cancer xenografts were injected with 0.74–18.5 MBq of the 90Y-labeled GRPr antagonist DOTA-AR and underwent in vivo and ex vivo CLI at 1–48 h after injection. After imaging, animals were sacrificed, their tumors and organs were harvested, and the activity concentration was measured by liquid scintillation counting. In a second set of experiments, Cerenkov photon counts for tumor and kidney on in vivo CLI were converted to activity concentrations using conversion factors determined from the first set of experiments. Results 90Y-DOTA-AR concentration in the 3 tumor models ranged from 0.5% to 4.8% of the injected activity per gram at 1 h after injection and decreased to 0.05%–0.15 injected activity per gram by 48 h after injection. A positive correlation was found between tumor activity concentrations and in vivo CLI signal (r2 = 0.94). A similar correlation was found for the renal activity concentration and in vivo Cerenkov luminescence (r2 = 0.98). Other organs were not distinctly visualized on the in vivo images, but ex vivo CLI was also correlated with the radioactivity concentration (r2 = 0.35–0.94). Using the time–activity curves from the second experiment, we calculated radiation doses to tumor and kidney of 0.33 ± 0.12 (range, 0.21–0.66) and 0.06 ± 0.01 (range, 0.05–0.08) Gy/MBq, respectively. Conclusion CLI is a promising, low-cost modality to measure individual radiation doses of 90Y-labeled compounds non-invasively. The use of Cerenkov imaging is expected to facilitate the development and comparison of 90Y-labeled compounds for targeted radiotherapy.

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“…Based on these findings, radioembolization is recommended in the guidelines from the European Society of Medical Oncology (ESMO) for patients with liver-limited metastases in whom the available chemotherapeutic options have failed [2]. 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].…”

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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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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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Survival Outcomes of a Salvage Patient Population after Radioembolization of Hepatic Metastases with Yttrium-90 Microspheres

Cited by 31 publications

References 34 publications

Pretreatment tumor volume as a prognostic factor in metastatic colorectal cancer treated with selective internal radiation to the liver using yttrium-90 resin microspheres

Pretreatment tumor volume as a prognostic factor in metastatic colorectal cancer treated with selective internal radiation to the liver using yttrium-90 resin microspheres

Cerenkov Luminescence Imaging for Radiation Dose Calculation of a ⁹⁰Y-Labeled Gastrin-Releasing Peptide Receptor Antagonist

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

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Survival Outcomes of a Salvage Patient Population after Radioembolization of Hepatic Metastases with Yttrium-90 Microspheres

Cited by 31 publications

References 34 publications

Pretreatment tumor volume as a prognostic factor in metastatic colorectal cancer treated with selective internal radiation to the liver using yttrium-90 resin microspheres

Pretreatment tumor volume as a prognostic factor in metastatic colorectal cancer treated with selective internal radiation to the liver using yttrium-90 resin microspheres

Cerenkov Luminescence Imaging for Radiation Dose Calculation of a 90Y-Labeled Gastrin-Releasing Peptide Receptor Antagonist

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

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Cerenkov Luminescence Imaging for Radiation Dose Calculation of a ⁹⁰Y-Labeled Gastrin-Releasing Peptide Receptor Antagonist