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 .
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.
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.