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Background and Objectives: The focus of this study was to demonstrate the application of our finite element method (FEM) to guide light dosimetry for I-PDT of locally advanced VX2 carcinoma.
Methods: VX2 carcinoma was surgically implanted in either the sternomastoid muscle of the neck (n = 6) or the biceps femoris of the thigh (n = 8) of New Zealand White rabbits. Periodic computerized tomography scans were used to assess tumor growth. Once the VX2 tumors reached a volume of approximately 3-15 cm^3, our image-based FEM was used to develop individualized treatment plans for I-PDT to deliver our recently suggested threshold intratumoral light irradiance and fluence (1). I-PDT was performed with 630-nm light that was administered 24 hours after injection of 5 mg/kg porfimer sodium. In several of the VX2 tumors, multiple sessions of consecutive light illumination were required to deliver the threshold light irradiance and the FEM was adjusted to simulate these treatments. Light dosimetry measurements were taken during treatment to monitor the intratumoral irradiance and fluence.
Results: Six rabbits had no tumor recurrence within 6-12 weeks post I-PDT. Eight rabbits experienced local control, but were euthanized before the end of the study period due to either metastasis or infection. Tumor metastasis was often observed prior to treatment. Normal tissue damage was observed and managed in some rabbits. There were no treatment related deaths.
Conclusions: Our results suggest that our FEM-based treatment planning can be applied in the safe and effective delivery of I-PDT to locally advanced cancers. This work is currently being translated into a clinical study.
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. 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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