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经动脉注入90钇微球的选择性内放射治疗不可切除肝细胞癌

Selective internal radiation therapy for nonresectable hepatocellular carcinoma with intraarterial infusion of 90yttrium microspheres.

作者信息

Lau W Y, Ho S, Leung T W, Chan M, Ho R, Johnson P J, Li A K

机构信息

Department of Surgery, Prince of Wales Hospital, Shatin, New Territories, Hong Kong.

出版信息

Int J Radiat Oncol Biol Phys. 1998 Feb 1;40(3):583-92. doi: 10.1016/s0360-3016(97)00818-3.

Abstract

PURPOSE

To evaluate the efficacy of intraarterial 90yttrium (90Y) microspheres in nonresectable hepatocellular carcinoma (HCC).

METHODS AND MATERIALS

Patients with nonresectable HCC, but without extrahepatic disease, who also had lung shunting < 15% and tumor-to-normal ratio > or =2, as determined by simulation using (99m)technetium macroaggregated albumin, were entered into the study. The radiation dose delivered to the lungs, tumor, and normal liver was estimated by a partition model. 90Y microspheres were infused into the hepatic artery at the time of hepatic angiography or through an implanted arterial portacatheter under fluoroscopy. Repeated treatments were given for residual or recurrent tumor. Response to treatment was monitored by serum alpha-fetoprotein or ferritin levels, together with serial computed tomography.

RESULTS

Seventy-one patients, including 20 patients with postoperative recurrence, were initially treated with an activity of 0.8 to 5.0 Giga-Becquerel (GBq) (21.6-135.1 mCi) (median 3.0 GBq or 81.1 mCi) of 90Y microspheres. There was a 50% reduction in tumor volume in 19 (26.7%) patients after the first treatment. However, the overall objective response in terms of changes in alpha-fetoprotein levels was 89% [partial response (PR) 67%, complete response (CR) 22%] among the 46 patients with raised pretreatment levels. The serum ferritin level in the other 25 patients dropped by 34 to 99% after treatment. Treatment was repeated in 15 patients. The maximum number of treatments was 5 and the maximum total activity was 13.0 GBq (351.4 mCi), given in 3 treatments. The estimated radiation doses to the nontumorous liver ranged from 25 to 136 Gy (median 52 Gy) in the first treatment and the highest total radiation dose was estimated to be 324 Gy. For the tumors, the estimated radiation doses ranged from 83 to 748 Gy (median 225 Gy) in the initial treatment and the highest cumulative dose reached was 1580 Gy. The residual tumors were resected in 4 patients. Two of these had complete histological remission, but only occasional viable tumor cells were found in the necrotic centers of the tumors resected from the other 2 patients. The median survival of the 71 patients was 9.4 months (range 1.8 to 46.4 months). Treatment was well tolerated and there was no bone-marrow toxicity, or clinical evidence of radiation hepatitis or pneumonitis.

CONCLUSIONS

Selective internal radiation therapy using 90Y microspheres is effective for selected cases of nonresectable HCC and is well tolerated. The objective response rate in terms of drop in tumor marker levels is higher than that based on reduction in tumor volume shown by computed tomography. The nontumorous liver appears more tolerant to internal radiation than external beam radiation. Selective internal radiation treatment may convert nonresectable tumors to resectable ones.

摘要

目的

评估动脉内注射90钇(90Y)微球治疗不可切除肝细胞癌(HCC)的疗效。

方法与材料

不可切除但无肝外疾病、经(99m)锝标记的聚合白蛋白模拟测定肺分流<15%且肿瘤与正常组织比值>或=2的HCC患者纳入本研究。通过分区模型估算肺部、肿瘤及正常肝脏所接受的辐射剂量。在肝血管造影时或经透视通过植入的动脉导管将90Y微球注入肝动脉。对残留或复发性肿瘤进行重复治疗。通过血清甲胎蛋白或铁蛋白水平以及连续的计算机断层扫描监测治疗反应。

结果

71例患者,包括20例术后复发患者,最初接受了活度为0.8 - 5.0吉贝可(GBq)(21.6 - 135.1毫居里)(中位值3.0 GBq或81.1毫居里)的90Y微球治疗。首次治疗后19例(26.7%)患者肿瘤体积缩小50%。然而,在46例治疗前甲胎蛋白水平升高的患者中,总体客观反应率(根据甲胎蛋白水平变化)为89%[部分缓解(PR)67%,完全缓解(CR)22%]。另外25例患者治疗后血清铁蛋白水平下降了34%至99%。15例患者接受了重复治疗。最多治疗5次,最大总活度为13.0 GBq(351.4毫居里),分3次给予。首次治疗时,非肿瘤肝脏所接受的估计辐射剂量范围为25至136戈瑞(中位值52戈瑞),最高总辐射剂量估计为324戈瑞。对于肿瘤,首次治疗时估计辐射剂量范围为83至748戈瑞(中位值225戈瑞),累积最高剂量达1580戈瑞。4例患者切除了残留肿瘤。其中2例有完全组织学缓解,但从另外2例患者切除的肿瘤坏死中心仅偶尔发现存活肿瘤细胞。71例患者的中位生存期为9.4个月(范围1.8至46.4个月)。治疗耐受性良好,未出现骨髓毒性,也无放射性肝炎或肺炎的临床证据。

结论

使用90Y微球的选择性内放射治疗对部分不可切除HCC病例有效且耐受性良好。基于肿瘤标志物水平下降的客观反应率高于基于计算机断层扫描显示的肿瘤体积缩小的反应率。非肿瘤肝脏对内放射的耐受性似乎高于外照射。选择性内放射治疗可能使不可切除肿瘤转变为可切除肿瘤。

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