Program in Molecular Therapeutics, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA.
Digestive Disease & Surgery Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
BMC Cancer. 2019 Jun 24;19(1):614. doi: 10.1186/s12885-019-5777-z.
Malignant pleural effusion (MPE) is a devastating sequela associated with cancer. Talc pleurodesis is a common treatment strategy for MPE but has been estimated to be unsuccessful in up to 20-50% of patients. Clinical failure of talc pleurodesis is thought to be due to poor dispersion. This monograph reports the development of a foam delivery system designed to more effectively coat the pleural cavity.
C57BL/6 mice were injected with Lewis lung carcinoma (LL/2) cells intrapleurally to induce MPE. The mice then received either normal saline (NS) control, foam control (F), talc slurry (TS, 2 mg/g) or talc foam (TF, 2 mg/g). Airspace volume was evaluated by CT, lungs/pleura were collected, and percent fibrosis was determined.
The TF group had significantly better survival than the TS group (21 vs 13.5 days, p < 0.0001). The average effusion volume was less in the talc groups compared to the control group (140 vs 628 μL, p < 0.001). TF induced significant lung fibrosis (p < 0.01), similar to TS. On CT, TF significantly (p < 0.05) reduced loss of right lung volume (by 30-40%) compared to the control group. This was not seen with TS (p > 0.05).
This report describes using a novel talc foam delivery system for the treatment of MPE. In the LL/2 model, mice treated with the TF had better survival outcomes and less reduction of lung volume than mice treated with the standard of care TS. These data provide support for translational efforts to move talc foam from animal models into clinical trials.
恶性胸腔积液（MPE）是癌症相关的毁灭性后遗症。滑石粉胸膜固定术是治疗 MPE 的常用策略，但据估计，多达 20-50%的患者治疗无效。滑石粉胸膜固定术的临床失败被认为是由于分散不良所致。本专论报告了一种泡沫输送系统的开发，旨在更有效地覆盖胸膜腔。
C57BL/6 小鼠经胸膜内注射 Lewis 肺癌（LL/2）细胞诱导 MPE。然后，小鼠接受生理盐水（NS）对照、泡沫对照（F）、滑石粉混悬液（TS，2mg/g）或滑石粉泡沫（TF，2mg/g）治疗。通过 CT 评估气腔容积，收集肺/胸膜，并确定纤维化百分比。
TF 组的存活率明显优于 TS 组（21 天 vs 13.5 天，p<0.0001）。与对照组相比，滑石粉组的胸腔积液量明显减少（140 比 628μL，p<0.001）。TF 诱导了明显的肺纤维化（p<0.01），与 TS 相似。在 CT 上，与对照组相比，TF 显著（p<0.05）减少了右肺容积的丧失（减少 30-40%）。TS 组未见此现象（p>0.05）。
本报告描述了使用新型滑石粉泡沫输送系统治疗 MPE。在 LL/2 模型中，用 TF 治疗的小鼠的生存结果更好，肺容积减少程度低于用标准治疗 TS 治疗的小鼠。这些数据为将滑石粉泡沫从动物模型转化为临床试验提供了支持。
