ABSTRACT
Objective To determine the optimized fractionated radiation schedule by comparing the dose-response relationship between different fractionated radiation schedules with a total dose of 40 Gy or 60 Gy in subclinical breast tumor.Methods Balb/c nude mice bearing subclinical human breast cancer (injected subcutaneously into the hind legs with 1.5 × 105 or 3.1 × 105 exponentially growing MCF-7 cells) were assigned randomly to blank control group (without radiation),conventionally fractionated radiation group (200 cGy,once daily,10 times/week),hyperfractionated radiation group (160 cGy,twice daily with an interval of 6 h,5 times/week),first hypofractionated radiation group (300 cGy,once daily,5 times/ week),and second hypofractionated radiation group (400 cGy,once every other day,3 times/week) ;the total dose was 40 Gy or 60 Gy.The measurement indices were tumor formation rate,short-term tumor control rate,long-term tumor control rate,the time of tumor recurrence,and the maximum diameter of the bottom of tumor.The observation lasted 24 weeks.Data were compared between these groups by chi-square test.Results With a total dose of 40 Gy (the number of injected cells was 1.5 × 105,the tumor formation rate of the blank control group was 2/8),hyperfractionated radiation was the optimized schedule.With a total dose of 60 Gy (the number of injected cells was 3.1 × 105,the tumor formation rate of the blank control group was 11/11),the first hypofractionated radiation (300 cGy,once daily,5 times/week) was the optimized schedule (P =0.001);the short-term and long-term tumor control rates of the conventionally fractionated radiation group,hyperfractionated radiation group,second hypofractionated radiation group,and first hypofractionated radiation group were 0/0 (tumor formation rates:8/8 and 8/8),50％/25％ (tumor formation rates:4/8 and 6/8),25 ％/25 ％ (tumor formation rates:6/8 and 6/8)),and 67 ％/67 ％ (tumor formation rates:4/12 and 4/12),respectively.Conclusions The optimized fractionated radiation schedule for subclinical breast cancer and its total dose vary with the number of injected tumor cells.When the tumor formation rate is 100％,hypofractionated radiation (300 cGy,once daily,5 times/week) is the optimized schedule in terms of long-term tumor control.
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Objective To study dose-response relationship and screen the optimized fractionated irradiation schedules in subclinical tumors of malignant glioma.Methods Balb/c-nude mice bearing human malignant glioma xenograft were assigned randomly into control group,fractionated irradiation schedules group and nimotuzumab-conventional fraction group.The fractionated schedules were 200 cGy x 5f/w,300 cGy ×5f/w,160 cGy ×2f/d x5 d and 400 cGy ×3f/w with total dose of 40 Gy and 60 Gy,respectively.Measurement indexes were tumor-forming rate,average recurrence time and maximum diameter of the tumor bottom.The observation lasted 24 weeks.Results With the total dose of 40 Gy,none of the significant long-term tumor regression were detected in any fractionated irradiation schedules; 400 cGy x 3f/w with complete tumor response at the end of treatment showed a better short-term curative effect.With the total dose of 60 Gy,long-term control rate of each fractionated irradiation schedule group was improved with prolonged average recurrence time of varable degrees,except 200 cGy x 5f/w fractionated schedule (tumor formation rate was 100％ at the end of treatment and average recurrence time was the poorest of 108 d).160 cGy × 2f/d × 5 d fractionated schedule showed the best curative effect with no tumor formation in 2 of 8 mice and longest recurrence time of 143 d.300 cGy x 5f/w fractionated schedule ranked second with no tumor formation in 1 of 8 mice and average recurrence time was 137 d.400 cGy x 3f/w fractionated schedule produced the poorest outcome with no case cured.There were no significant changes in the tumor-forming rate or average recurrence time when nimotuzumab was concurrently used for subclinical tumors of malignant glioma with total dose of 60 Gy.Conclusions Conventional fractionated irradiation is not the best option to control the sustained growth.160 cGy ×2f/d ×5 d and 300 cGy × 5f/w might be the optimized fractionated irradiation schedules for subclinical tumors of malignant glioma.
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Objective To evaluate the radiobiological effect of different irradiation fractionated regimens in human glioma cells ( BT 325 cell line). Methods The xenografts in Balb/c-nude mice were irradiated with different single and fractionated regimens. The single fraction dose was 10, 20, 30, 40 and 60 Gy, respectively. The fractionated regimens were 2 Gy × 5 fractions ( irradiated every day), and 3 Gy ×3 fractions (irradiated every other day), 3 Gy × 5 fractions (irradiated every day) and 4 Gy × 3 fractions (irradiated every other day), with total doses of 125 Gy, 114 Gy, 126 Gy and 112 Gy, respectively. The growth curve was used to evaluate the tumor doubling time. clonogenic assays was performed to draw the cell survival curve and analyze the radiobiological parameters with doses of 1, 2, 4, 6, 8 and 10 Gy. T1/2 was measured by comet assay. Results Tumor regression were not observed by single fraction irradiation, 2 Gy × 5 fractons and 3 Gy × 3 fractions irradiation regimens. The tumor regress was more significant with the increas of fraction dose. The 4 Gy × 3 fractionrs inhibited tumor more though not curing tumor. The cell doubling time of the BT 325 cell was 30. 16 h and the tumor doubling time of the xenograft was 43 days.When fitted with L-Q model ,α was 0. 36 Gy -1 and β was 0. 057 Gy -2. When fitted with the single-hit multitarget model, D0 was 1. 394 Gy, Dq was 2. 127 Gy and SF2 was 0. 714, respectively. The T1/2 was 9. 999min. Conclusions Glioma is a radioresistant tumor. Increase of the fraction dose improves recent effect.Further study is needed to control the tumor stem cells.
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PURPOSE: A ginkgo biloba extract (GBE) has been known as a hypoxic cell radiosensitizer. Its mechanisms of action are increase of the red blood cell deformability, decrease the blood viscosity, and decrease the hypoxic cell fraction in the tumor. The aims of this study were to estimate the effect of GBE on fractionated radiotherapy and to clarify the mechanism of action of the GBE by estimating the blood flow in tumor and normal muscle. MATERIALS AND METHODS: Fibrosarcoma (FSaII) growing in a C3H mouse leg muscle was used as the tumor model. When the tumor size reached 7 mm in diameter, the GBE was given intraperitoneally at 1 and 25 hours prior to irradiation. The tumor growth delay was measured according to the various doses of radiation (3, 6, 9, 12 Gy and 15 Gy) and to the fractionation (single and fractionated irradiation) with and without the GBE injection. The radiation dose to the tumor the response relationships and the enhancement ratio of the GBE were measured. In addition, the blood flow of a normal muscle and a tumor was compared by laser Doppler flowmetry according to the GBE treatment. RESULTS: When the GBE was used with single fraction irradiation with doses ranging from 3 to 12 Gy, GBE increased the tumor growth delay significantly (p<0.05) and the enhancement ratio of the GBE was 1.16. In fractionated irradiation with 3 Gy per day, the relationships between the radiation dose (D) and the tumor growth delay (TGD) were TGD (days)=0.26X D (Gy)+.13 in the radiation alone group, and the TGD (days)=0.30X D (Gy)+.13 in the radiation with GBE group. As a result, the enhancement ratio was 1.19 (95% confidence interval; 1.13~1.27). Laser Doppler flowmetry was used to measure the blood flow. The mean blood flow was higher in the muscle (7.78 mL/100 g/min in tumor and the 10.15 mL/100 g/min in muscle, p=0.0001) and the low blood flow fraction (less than 2 mL/100 g/min) was higher in the tumor (0.5% vs. 5.2%, p=0.005). The blood flow was not changed with the GBE in normal muscle, but was increased by 23.5% ( p=0.0004) in the tumor. CONCLUSION: Based on these results, it can be concluded that the GBE enhanced the radiation effect significantly when used with fractionated radiotherapy as well as with single fraction irradiation. Furthermore, the GBE increased the blood flow of the tumor selectively.