Clinical and experimental study on regional administration of phosphorus 32 glass microspheres in treating hepatic carcinoma.

AIM:To study the therapeutical effectiveness, dosage range and toxic adverse effects of domestic phosphorus 32 glass microsphere and evaluate its clinical significance.
METHODS: I.Fifty two BALB/c tumor bearing male nude mice were allocated into treatment group(n = 38) and control group(n = 14). In the former group different doses of (32) P-GMS were injected into the tumor mass, while in the latter (31)P-GMS or no treatment was given. The experimental animals were sacrificed in batches, and then the tumors and their nearby tissues were examined by light and electron microscopy.II. Through selective catheterization of hepatic artery, (32)P-GMS was infused to 5 healthy domestic pigs in a dosage equivalent to the therapeutic dose for human being, and (31)P-GMS was infused to another 5 healthy domestic pigs. Two pigs infused with contrast medium served as whole course blank controls. One pig from each group was surrendered to euthanasia at week 1, 4, 8 and 16 respectively. The ultrastructural histopath ological changes in liver tissues taken from different sites were evaluated semiquan titatively. III. One hundred and twenty seven times of (32)P-GMS intrahepatic artery interventional therapies were performed on 93 patients with hepatic carcinoma, including 79 cases of primary hepatic carcinoma and 14 cases of secondary hepatic carcinoma. (32)P-GMS (n = 30), and group B,(32)P-GMS and half dose of trans hepatic artery embolization (TAE)(n = 49), and 18 patients with HCC by TAE only as control group C. Fourteen patients with secondary hepatic carcinoma were treated in the same way as group B or C.
RESULTS: I.Comparing with the control group, the treatment group of tumor bearing nude mice attained the tumor inhibition rates of 59.7%-93.7% (F = 579.62 P < 0.01) at 14d. At an absorbed dose of 7320Gy, the tumor cells were completely destroyed. When the absorbed doses ranged from 1830Gy to 3660Gy, most of the tumor cells showed the evidences of injury or necrosis, but there appeared some well differentiated tumor cells and enhanced effect of the autoimmunocytes. At an absorbed dose of 366Gy or less, some tumor cells still remained active prolix-ferative ability. The definite anticancer effect appeared as early as 3d after intratumoral injection of (32)P-GMS.II. The cumulative amount of (32) P-GMS in the target tissue after trans hepatic artery instillation attained more than 90% of the total dose administrated. Semiquantitative analysis of ultrastructral morphology in the experimental group showed no statistical difference between the nuclear abnormality (N(abn)) and mitochondrial variability (M(var)) at week 1 or 2, but revealed prominent difference (X(2) = 6.70-9.68, P < 0.01, X(2) = 65.09-115.09, P <0.001) as compared with those in the other groups. In the experimental group the N abn in tissues showed no significant difference between week 8 and week 16. No apparent changes were found in the stomach, spleen, kidney and lung tissues of the experimental pigs. III. The therapeutical results of HCC patients in group A were closely approximated to those of group C, no hematological toxic side effects were noted, and the systemic reaction was mild. In some patients 2mos-3mos after treatment some secondary foci appeared around the periphery of the primary lesion. In general better effectiveness was obtained in patients with small lesion. After analyzing by RIDIT method, the therapeutic result in group B was significantly better than that in group C, and secondary foci around the original lesion were rarely seen at 3mos after treatment. In group C the collateral circulation was reestablished along the periphery of primary foci and the secondary foci appeared more frequently, and were required to undergo several courses of treatment. In group B, 4 cases of HCC were treated surgically as their mass decreased in size after (32)P-GMS treatment.Resected specimens showed that the tumor was encapsulated by fibrotic tissue and most of the tumor cells necrosed. The 3 year survival rates were 43.3%-51.0% after A and B regimen treatment. In 14 cases of secondary HCC, the foci were well controled within one year after treatment.
CONCLUSION: When the experimental model of implanted human liver cancer cells received (32)P-GMS of 1830Gy-3660Gy, it produced excellent anticancer effect without any injury to the normal neighboring tissues and the prominent anticancer effect was shown within 3d after intratumoral injection. Intrahepatic arterial administration of (32)P-GMS at the macro-cosmic absorbed dosage less than 190 Gy/dose exerted reversible sub lethal injury to domestic pig liver tissues. It took more than 8 weeks to repair the injured liver tissue and restore its function.(32)P-GMS trans hepatic artery embolization is an effective and safe regimen in treating hepatic carcinoma.