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An experimental evaluation of three preoperative radiation regimens for resectable rectal cancer
Authors:Genc Basha MD   PhD  Willy Landuyt SrSc  Jack Fowler PhD  Dirk Vordermark MD   PhD  Karin Haustermans MD   PhD  Karel Geboes MD   PhD  Walter Van den Bogaert MD   PhD  Sing Hiem Yap MD   PhD  Philippe Lambin MD   PhD  Freddy Penninckx MD   PhD
Affiliation:(1) Department of Abdominal Surgery, University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium;(2) Department of Radiobiology/Radiotherapy, University Hospital Gasthuisberg, Katholieke Universiteit, Leuven, Belgium;(3) Department of Pathology, University Hospital Gasthuisberg, Katholieke Universiteit, Leuven, Belgium;(4) Department of Hepatology, University Hospital Gasthuisberg, Katholieke Universiteit, Leuven, Belgium;(5) Department of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Abstract:Background We investigated the degree of tumor cell killing after radiotherapy regimens commonly used in clinical practice in comparison with an accelerated schedule. Methods Mtln3 mammary adenocarcinoma tumor cells were inoculated subcutaneously in the hind leg of syngeneic Fischer 344 rats. Tumors were irradiated with 5×5 Gy in 5 days, 10×3 Gy over 10 days, or 5×(2×3) Gy in 5 days. After excision of the irradiated tumors, the dye exclusion, a tetrazolium-based colorimetric and the clonogenic assays were used to determine tumor cell viability and surviving fractions. Results Estimated potential doubling time values indicate a rapid proliferation capacity, comparable with potential doubling time values in human rectal cancer. The dye exclusion and clonogenic assays revealed a significantly higher degree of cell killing after the hypofractionated and the accelerated regimens of, respectively, 5×5 Gy and 5×(2×3) Gy over 5 days compared with 10×3 Gy over 10 days. Conclusions A shorter treatment time offered the best therapeutic efficacy. The schedule involving two daily fractions of 3 Gy over 5 days should be less toxic than 5×5 Gy and may therefore provide a therapeutic advantage.
Keywords:Rectal carcinoma  Preoperative irradiation  Total treatment time  Fractionation  Tumor cell proliferation
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