Jermyn Michael, Davis Scott C, Dehghani Hamid, Huggett Matthew T, Hasan Tayyaba, Pereira Stephen P, Bown Stephen G, Pogue Brian W
Thayer School of Engineering, Dartmouth College, Hanover, NH-03755, USA.
Phys Med Biol. 2014 Apr 21;59(8):1911-21. doi: 10.1088/0031-9155/59/8/1911. Epub 2014 Mar 20.
The goal of this study was to determine dominant factors affecting treatment response in pancreatic cancer photodynamic therapy (PDT), based on clinically available information in the VERTPAC-01 trial. This trial investigated the safety and efficacy of verteporfin PDT in 15 patients with locally advanced pancreatic adenocarcinoma. CT scans before and after contrast enhancement from the 15 patients in the VERTPAC-01 trial were used to determine venous-phase blood contrast enhancement and this was correlated with necrotic volume determined from post-treatment CT scans, along with estimation of optical absorption in the pancreas for use in light modeling of the PDT treatment. Energy threshold contours yielded estimates for necrotic volume based on this light modeling. Both contrast-derived venous blood content and necrotic volume from light modeling yielded strong correlations with observed necrotic volume (R² = 0.85 and 0.91, respectively). These correlations were much stronger than those obtained by correlating energy delivered versus necrotic volume in the VERTPAC-01 study and in retrospective analysis from a prior clinical study. This demonstrates that contrast CT can provide key surrogate dosimetry information to assess treatment response. It also implies that light attenuation is likely the dominant factor in the VERTPAC treatment response, as opposed to other factors such as drug distribution. This study is the first to show that contrast CT provides needed surrogate dosimetry information to predict treatment response in a manner which uses standard-of-care clinical images, rather than invasive dosimetry methods.
本研究的目的是基于VERTPAC - 01试验中的临床可用信息,确定影响胰腺癌光动力疗法(PDT)治疗反应的主要因素。该试验调查了维替泊芬PDT对15例局部晚期胰腺腺癌患者的安全性和有效性。利用VERTPAC - 01试验中15例患者增强前后的CT扫描来确定静脉期血液增强情况,并将其与治疗后CT扫描确定的坏死体积相关联,同时估计胰腺中的光吸收以用于PDT治疗的光建模。基于此光建模,能量阈值轮廓得出坏死体积的估计值。对比衍生的静脉血含量和光建模得出的坏死体积与观察到的坏死体积均具有很强的相关性(R²分别为0.85和0.91)。这些相关性比在VERTPAC - 01研究以及先前一项临床研究的回顾性分析中通过关联递送的能量与坏死体积所获得的相关性要强得多。这表明对比CT可以提供关键的替代剂量学信息来评估治疗反应。这也意味着光衰减可能是VERTPAC治疗反应中的主要因素,而非其他因素,如药物分布。本研究首次表明,对比CT以使用标准护理临床图像而非侵入性剂量学方法的方式,提供了预测治疗反应所需的替代剂量学信息。