Pretreatment planning and light dosimetry for interstitial PDT of locally advanced cancer (Conference Presentation)

G. Shafirstein, D. Bellnier, Emily Oakley, M. Habitzruther, Hannah Cooper, Sarah Chamberlain, Sasheen Hamilton, A. Hutson, S. Sexton, Leslie I Curtin, J. Spernyak, Steven G. Turowski, H. Arshad, Lawrence Tworek, M. Mallory, B. Henderson
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Abstract

Pretreatment Planning and Light Dosimetry for Interstitial PDT of Locally Advanced Cancer Gal Shafirstein¹, David Bellnier¹, Emily Oakley¹, Michael Habitzruther¹, Sasheen Hamilton¹, Hannah Cooper¹, Sarah Chamberlain1, Alan Hutson2, Sandra Sexton3, Leslie Curtin3, Joe Spernyak4, Steven Turowski4, Hassan Arshad5, Lawrence Tworek¹, Matthew Mallory¹ and Barbara Henderson1. ¹ Photodynamic Therapy Center at the Department of Cell Stress Biology, and ² Department of Biostatistics and Bioinformatics, 3Laboratory Animals Shared Resources, 4Translational Imaging Shared Resource, 5Department of Head and Neck Surgery. Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA Objective: To highlight the critical need for pretreatment planning and light dosimetry in administering interstitial photodynamic therapy (I-PDT) in the treatment of locally advanced cancer (LAC). Background: There is no effective standard treatment for LAC that failed to respond to surgery and chemo-radiation. The newest immunotherapies are effective in only 5-16% of the cases. I-PDT can be considered if the target tumor does not invade a major blood vessel, and the tumor is accessible to fiber-optic placement. Multiple fibers are required for interstitial illumination of the target tumor and margins. Image-based pretreatment planning is used to determine the number and proposed location of fibers. Light dosimetry is employed to measure intratumoral light fluence and irradiance. To date, it was acceptable that a threshold intratumoral light fluence is required for adequate response. Whereas, we demonstrated that intratumoral light irradiance impacts tumor response [1]. Overview: This talk will present an image-based finite element method (FEM) approach for guiding I-PDT. We will discuss the importance of delivering a threshold intratumoral light irradiance in addition to threshold fluence. We will demonstrate that even if a threshold fluence is delivered, an inadequate intratumoral irradiance will result in poor response. We will reveal that adequate light irradiance and fluence can yield up to 90% cure rate in mice and excellent local control in rabbits with LAC. We will present our image-based FEM and light dosimetry approach to translate the preclinical findings to test I-PDT in the treatment of patients with locally advanced head and neck cancer. References 1.Shafirstein G, Bellnier DA, Oakley E, Hamilton S, Habitzruther M, Tworek L, Hutson A, Spernyak JA, Sexton S, Curtin L, Turowski SG, Arshad H, Henderson B. Irradiance controls photodynamic efficacy and tissue heating in experimental tumours: implication for interstitial PDT of locally advanced cancer. Br J Cancer. 2018;119(10):1191-9. Acknowledgements: Supported in part by NCI/NIH R01 CA193610 to GS, P01CA55791 to Sandra Gollnick, and by Roswell Park Comprehensive Cancer Center Support Grant P30CA16056. We thank Diane Filippini and Raymond Wasielewski for their assistance in obtaining the CT scans and Dr. Craig Hendler MD for conducting diagnosis of the CT scans. We thank the staff of Laboratory Animal Shared Resource at Roswell Park. We thank Concordia Laboratories Inc. for providing the Photofrin® at no cost.
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局部晚期肿瘤间质PDT的预处理计划和光剂量测定(会议报告)
局部晚期肿瘤间质PDT的预处理计划与光剂量学研究[al Shafirstein¹,David Bellnier¹,Emily Oakley¹,Michael Habitzruther¹,Sasheen Hamilton¹,Hannah Cooper¹,Sarah Chamberlain1, Alan Hutson2, Sandra Sexton3, Leslie Curtin3, Joe Spernyak4, Steven Turowski4, Hassan Arshad5, Lawrence Tworek¹,Matthew Mallory¹,Barbara Henderson1]。1细胞应激生物学系光动力治疗中心,2生物统计与生物信息学学系,3实验动物共享资源,4转化成像共享资源,5头颈外科。目的:强调在局部晚期癌症(LAC)治疗中给予间质性光动力治疗(I-PDT)的预处理计划和光剂量学的关键需求。背景:对于手术和放化疗无效的LAC没有有效的标准治疗方法。最新的免疫疗法仅对5-16%的病例有效。如果目标肿瘤没有侵犯主要血管,并且肿瘤易于光纤放置,则可以考虑I-PDT。需要多种纤维来照亮肿瘤间质和边缘。基于图像的预处理规划用于确定纤维的数量和建议的位置。光剂量法用于测量肿瘤内的光影响和辐照度。迄今为止,可以接受的是,需要一个阈值的肿瘤内光影响才能产生充分的反应。然而,我们证明了肿瘤内光辐照度影响肿瘤反应[1]。概述:本次演讲将介绍一种基于图像的有限元方法(FEM)来指导I-PDT。除了阈值影响外,我们还将讨论提供阈值肿瘤内光辐照度的重要性。我们将证明,即使提供了阈值,瘤内辐照度不足也会导致不良反应。我们将揭示,适当的光照和影响可以在小鼠中产生高达90%的治愈率,并在患有LAC的兔子中产生良好的局部控制。我们将介绍基于图像的FEM和光剂量法方法,将临床前研究结果转化为I-PDT治疗局部晚期头颈癌患者的测试。References1。Shafirstein G, Bellnier DA, Oakley E, Hamilton S, Habitzruther M, Tworek L, Hutson A, Spernyak JA, Sexton S, Curtin L, Turowski SG, Arshad H, Henderson B.辐照对局部晚期肿瘤间质PDT的影响。中国生物医学工程学报,2018;39(5):391 - 391。致谢:部分由NCI/NIH R01 CA193610 to GS, P01CA55791 to Sandra Gollnick和Roswell Park综合癌症中心支持基金P30CA16056支持。我们感谢Diane Filippini和Raymond Wasielewski对CT扫描的帮助,感谢Craig Hendler博士对CT扫描的诊断。我们感谢罗斯威尔公园实验动物共享资源的工作人员。我们感谢Concordia Laboratories Inc.免费提供Photofrin®。
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