Duke University Medical Center, Durham, NC 27710, USA.
Med Phys. 2012 Mar;39(3):1170-81. doi: 10.1118/1.3679839.
A recently completed Phase I clinical trial combined concurrent Mitomycin-C chemotherapy with deep regional heating using BSD-2000 Sigma-Ellipse applicator (BSD Corporation, Salt Lake City, UT, U.S.A.) for the treatment of nonmuscle invasive bladder cancer. This work presents a new treatment planning approach, and demonstrates potential impact of this approach on improvement of treatment quality.
This study retrospectively analyzes a subset of five patients on the trial. For each treatment, expert operators selected "clinical-optimal" settings based on simple model calculation on the BSD-2000 control console. Computed tomography (CT) scans acquired prior to treatment were segmented to create finite element patient models for retrospective simulations with Sigma-HyperPlan (Dr. Sennewald Medizintechnik GmbH, Munchen, Germany). Since Sigma-HyperPlan does not account for the convective nature of heat transfer within a fluid filled bladder, an effective thermal conductivity for bladder was introduced. This effective thermal conductivity value was determined by comparing simulation results with clinical measurements of bladder and rectum temperatures. Regions of predicted high temperature in normal tissues were compared with patient complaints during treatment. Treatment results using "computed-optimal" settings from the planning system were compared with clinical results using clinical-optimal settings to evaluate potential of treatment improvement by reducing hot spot volume.
For all five patients, retrospective treatment planning indicated improved matches between simulated and measured bladder temperatures with increasing effective thermal conductivity. The differences were mostly within 1.3 °C when using an effective thermal conductivity value above 10 W/K/m. Changes in effective bladder thermal conductivity affected surrounding normal tissues within a distance of ∼1.5 cm from the bladder wall. Rectal temperature differences between simulation and measurement were large due to sensitivity to the sampling locations in rectum. The predicted bladder T90 correlated well with single-point bladder temperature measurement. Hot spot locations predicted by the simulation agreed qualitatively with patient complaints during treatment. Furthermore, comparison between the temperature distributions with clinical and computed-optimal settings demonstrated that the computed-optimal settings resulted in substantially reduced hot spot volumes.
Determination of an effective thermal conductivity value for fluid filled bladder was essential for matching simulation and treatment temperatures. Prospectively planning patients using the effective thermal conductivity determined in this work can potentially improve treatment efficacy (compared to manual operator adjustments) by potentially lower discomfort from reduced hot spots in normal tissue.
最近完成的一项 I 期临床试验将米托蒽醌化疗与 BSD-2000 Sigma-Ellipse 施源器（美国犹他州盐湖城 BSD 公司）的深部区域性加热相结合，用于治疗非肌肉浸润性膀胱癌。本研究提出了一种新的治疗计划方法，并证明了该方法在提高治疗质量方面的潜在影响。
本研究回顾性分析了试验中的五名患者亚组。对于每次治疗，专家操作人员根据 BSD-2000 控制台的简单模型计算，选择“临床最佳”设置。在治疗前获取的计算机断层扫描（CT）扫描用于创建有限元患者模型，以进行 Sigma-HyperPlan（德国慕尼黑 Dr. Sennewald Medizintechnik GmbH）的回顾性模拟。由于 Sigma-HyperPlan 没有考虑充满液体的膀胱内热量传递的对流性质，因此引入了膀胱的有效导热系数。通过将模拟结果与膀胱和直肠温度的临床测量值进行比较，确定了这个有效导热系数值。将正常组织中预测的高温区域与治疗过程中患者的抱怨进行比较。使用规划系统的“计算最佳”设置与使用临床最佳设置的临床结果进行比较，以评估通过减少热点体积来改善治疗的潜力。
对于所有五名患者，回顾性治疗计划表明，随着有效导热系数的增加，模拟和测量的膀胱温度之间的匹配得到了改善。当使用大于 10 W/K/m 的有效导热系数时，差异大多在 1.3°C 以内。有效膀胱导热系数的变化会影响膀胱壁 1.5 厘米范围内的周围正常组织。由于直肠内采样位置的敏感性，直肠温度测量的模拟和测量之间的差异很大。膀胱 T90 的预测与单点膀胱温度测量很好地相关。模拟预测的热点位置与治疗过程中的患者抱怨定性一致。此外，临床和计算最佳设置的温度分布比较表明，计算最佳设置导致热点体积显著减少。
确定充满液体的膀胱的有效导热系数对于匹配模拟和治疗温度至关重要。使用本研究中确定的有效导热系数对患者进行前瞻性规划，通过减少正常组织中热点的减少，可能会降低患者的不适感，从而提高治疗效果（与手动操作人员调整相比）。
