INSERM U836, Equipe 6, ESRF, Medical Beamline, BP 220, 38043, Grenoble Cedex 9, France.
J Neurooncol. 2010 Jul;98(3):287-95. doi: 10.1007/s11060-009-0074-3. Epub 2009 Dec 11.
We have evaluated the efficacy of intracerebral (i.c.) convection-enhanced delivery (CED) of cisplatin in combination with photon irradiation for the treatment of F98 glioma-bearing rats. One thousand glioma cells were stereotactically implanted into the brains of Fischer rats and 13 days later cisplatin (6 microg/20 microl) was administered i.c. by CED at a flow rate of 0.5 microl/min. On the following day the animals were irradiated with a single 15 Gy dose of X-rays, administered by a linear accelerator (LINAC) or 78.8 keV synchrotron X-rays at the European Synchrotron Radiation Facility (ESRF). Untreated controls had a mean survival time (MST) + or - standard error of 24 + or - 1 days compared to >59 + or - 13 days for rats that received cisplatin alone with 13% of the latter surviving >200 days. Rats that received cisplatin in combination with either 6 MV (LINAC) or 78.8 keV (synchrotron) X-rays had almost identical MSTs of >75 + or - 18 and >74 + or - 19 days, respectively with 17 and 18% long-term survivors. Microscopic examination of the brains of long-term surviving rats revealed an absence of viable tumor cells and cystic areas at the presumptive site of the tumor. Our data demonstrate that i.c. CED of cisplatin in combination with external X-irradiation significantly enhanced the survival of F98 glioma-bearing rats. This was independent of the X-ray beam energy and probably was not due to the production of Auger electrons as we previously had postulated. Our data provide strong support for the approach of concomitantly administering platinum-based chemotherapy in combination with radiotherapy for the treatment of brain tumors. Since a conventional LINAC can be used as the radiation source, this should significantly broaden the clinical applicability of this approach compared to synchrotron radiotherapy, which could only be carried out at a very small number of specialized facilities.
我们评估了立体定向脑内（i.c.）顺铂对流增强递送（CED）联合光子照射治疗 F98 神经胶质瘤荷瘤大鼠的疗效。将 1000 个神经胶质瘤细胞立体定向植入 Fischer 大鼠脑内，13 天后以 0.5 μl/min 的流速通过 CED 脑内给予顺铂（6 μg/20 μl）。次日，用线性加速器（LINAC）或欧洲同步辐射装置（ESRF）的 78.8keV 同步加速器 X 射线对动物进行单次 15Gy 照射。未经治疗的对照组的平均生存时间（MST）±标准误差为 24±1 天，而单独接受顺铂治疗的大鼠 MST 为>59±13 天，其中 13%的大鼠存活时间超过 200 天。接受顺铂联合 6MV（LINAC）或 78.8keV（同步加速器）X 射线治疗的大鼠 MST 几乎相同，分别为>75±18 和>74±19 天，17%和 18%的大鼠长期存活。对长期存活大鼠的大脑进行显微镜检查显示，在肿瘤假定部位不存在存活的肿瘤细胞和囊状区域。我们的数据表明，立体定向脑内 CED 顺铂联合外照射显著提高了 F98 神经胶质瘤荷瘤大鼠的生存率。这与 X 射线束能量无关，可能不是我们之前假设的产生俄歇电子所致。我们的数据为同时给予铂类化疗联合放疗治疗脑肿瘤的方法提供了强有力的支持。由于传统的 LINAC 可作为放射源，与只能在少数专门设施进行的同步放射治疗相比，这将显著扩大该方法的临床适用性。
