and were given a second course of radiotherapy. The median follow-up period was 47.7 months (1.8 to 110.6) measured from the start of the reirradiation. IMRT of various types including conventional fractionation scheme, stereotactic radiotherapy, twice-daily (BID) radiation were used to deliver the second course of radiotherapy. The prescribed doses delivered from the different fractionation schemes were converted into Equivalent Dose at 2 Gy per fractions (EQD2) using a/b ratios of 10 Gy and 3 Gy for the disease and fatal complication respectively. The variations of the accrual local control and overall survival at 24 months versus the dose as well as the recurrent GTV volume were analyzed. The relationship between the fatal complication rate and the dose were also studied. Logistic regression was used to fit the dose and volume responses (if applicable) using a computer algorithm software. The significance of the responses were evaluated using the likelihood ratio test at a significance level of pZ0.05. Results: The dose delivered to the tumor ranged from 44.3 Gy to 72 Gy (EQD2). Local control and the rate of fatal complication appear to rise with the dose, but the relationships are not statistically significant (p Z 0.147 and pZ0.054 respectively). The overall survival rises with the dose until around 60 Gy (EQD2) and then falls again. The size of GTV varied significantly from 1.8 cc to 194 cc. The local control shows a significant decreasing trend with GTV volume (p<0.001). A similar trend can be seen on overall survival but has not reached statistical significance (pZ0.061). There is no clear trend or correlation between the fatal complication rate and the GTV volume. A multi-dimensional logistic model was also fitted to the local control versus the target dose and GTV volume. The result suggests that the local control is predominantly affected by the GTV volume as expected from the individual analyses. While local control also has an increasing trend with prescribed dose for smaller GTV, higher prescribed dose does not lead to higher control for large tumors, probably due to both the large tumor mass and the resulting deterioration of dose coverage in a recurrent radiotherapy setting. Conclusion: The GTV volume plays a significant role in the local control of the recurrent diseases. 60 Gy (EQD2) appears to be the optimal dose for achieving the best survival outcome while balancing the probability of local control and fatal complication, but a higher personalized dose based on the multi-dimensional logistic model might be considered for smaller tumors.
In this study, a transferrin/folic acid double-targeting graphene oxide drug delivery system loaded with doxorubicin was designed. Graphene oxide was prepared by ultrasound improved Hummers method and was modified with Pluronic F68, folic acid, and transferrin to decrease its toxicity and to allow dual-targeting. The results show that the double target drug delivery system (TFGP*DOX) has good and controllable drug delivery performance with no toxicity. Moreover, TFGP*DOX has a better inhibitory effect on SMMC-7721 cells than does a single target drug delivery system (FGP*DOX). The results of drug release analysis and cell inhibition studies showed that TFGP*DOX has a good sustained release function that can reduce the drug release rate in blood circulation over time and improve the local drug concentration in or near a targeted tumor. Therefore, the drug loading system (TFGP*DOX) has potential application value in the treatment of hepatocellular carcinoma.
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