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Low dose rate radiosensitization of hepatocellular carcinoma in vitro and in patients.
Cuneo, Kyle C; Davis, Mary A; Feng, Mary U; Novelli, Paula M; Ensminger, William D; Lawrence, Theodore S.
Afiliación
  • Cuneo KC; University of Michigan Medical Center, Department of Radiation Oncology, Ann Arbor, MI; Ann Arbor Veterans Affairs Hospital, Department of Radiation Oncology, Ann Arbor, MI. Electronic address: kcuneo@umich.edu.
  • Davis MA; University of Michigan Medical Center, Department of Radiation Oncology, Ann Arbor, MI.
  • Feng MU; University of Michigan Medical Center, Department of Radiation Oncology, Ann Arbor, MI.
  • Novelli PM; University of Michigan Medical Center, Department of Radiology, Ann Arbor, MI.
  • Ensminger WD; University of Michigan Medical Center, Department of Internal Medicine, Ann Arbor, MI.
  • Lawrence TS; University of Michigan Medical Center, Department of Radiation Oncology, Ann Arbor, MI.
Transl Oncol ; 7(4): 472-8, 2014 Aug.
Article en En | MEDLINE | ID: mdl-24956939
Transarterial radioembolization (TARE) with (90)Y microspheres delivers low dose rate radiation (LDR) to intrahepatic tumors. In the current study, we examined clonogenic survival, DNA damage, and cell cycle distribution in hepatocellular carcinoma (HCC) cell lines treated with LDR in combination with varying doses and schedules of 5-fluorouracil (5-FU), gemcitabine, and sorafenib. Radiosensitization was seen with 1 to 3 µM 5-FU (enhancement ratio 2.2-13.9) and 30 to 100 nM gemcitabine (enhancement ratio 1.9-2.9) administered 24 hours before LDR (0.26 Gy/h to 4.2 Gy). Sorafenib radiosensitized only at high concentrations (3-10 µM) when administered after LDR. For a given radiation dose, greater enhancement was seen with LDR compared to standard dose rate therapy. Summarizing our clinical experience with low dose rate radiosensitization, 13 patients (5 with HCC, 8 with liver metastases) were treated a total of 16 times with TARE and concurrent gemcitabine. Six partial responses and one complete response were observed with a median time to local failure of 7.1 months for all patients and 9.9 months for patients with HCC. In summary, HCC is sensitized to LDR with clinically achievable concentrations of gemcitabine and 5-FU in vitro. Encouraging responses were seen in a small cohort of patients treated with TARE and concurrent gemcitabine. Future studies are needed to validate the safety and efficacy of this approach.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Transl Oncol Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Transl Oncol Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos