Irradiance controls photodynamic efficacy and tissue heating in experimental tumours: implication for interstitial PDT of locally advanced cancer

Gal Shafirstein,Sasheen Hamilton,Emily Oakley,Steven G Turowski,Leslie Curtin,Sandra Sexton,Hassan Arshad,Barbara Henderson,Alan Hutson,David A Bellnier,Lawrence Tworek,Joseph A Spernyak,Michael Habitzruther

doi:10.1038/s41416-018-0210-y

Gal Shafirstein, Sasheen Hamilton + Show 11 more

Open Access

https://doi.org/10.1038/s41416-018-0210-y

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Journal: British journal of cancer	Publication Date: Oct 24, 2018
Citations: 36	License type: open-access

Affiliation: Roswell Park Cancer Institute

Abstract

BackgroundCurrently delivered light dose (J/cm2) is the principal parameter guiding interstitial photodynamic therapy (I-PDT) of refractory locally advanced cancer. The aim of this study was to investigate the impact of light dose rate (irradiance, mW/cm2) and associated heating on tumour response and cure.MethodsFinite-element modeling was used to compute intratumoural irradiance and dose to guide Photofrin® I-PDT in locally advanced SCCVII in C3H mice and large VX2 neck tumours in New Zealand White rabbits. Light-induced tissue heating in mice was studied with real-time magnetic resonance thermometry.ResultsIn the mouse model, cure rates of 70–90% were obtained with I-PDT using 8.4–245 mW/cm2 and ≥45 J/cm2 in 100% of the SCCVII tumour. Increasing irradiance was associated with increase in tissue heating. I-PDT with Photofrin® resulted in significantly (p < 0.05) higher cure rate compared to light delivery alone at same irradiance and light dose. Local control and/or cures of VX2 were obtained using I-PDT with 16.5–398 mW/cm2 and ≥45 J/cm2 in 100% of the tumour.ConclusionIn Photofrin®-mediated I-PDT, a selected range of irradiance prompts effective photoreaction with tissue heating in the treatment of locally advanced mouse tumour. These irradiances were translated for effective local control of large VX2 tumours.

Highlights

Delivered light dose (J/cm2) is the principal parameter guiding interstitial photodynamic therapy (I-PDT) of refractory locally advanced cancer
We report here the results from a preclinical study that elucidates and quantifies the impact of intratumoural irradiance on tumour response and cure, toxicity, and photothermal effects in I-PDT with Photofrin®
I-PDT represents a promising strategy for treating large, locally advanced cancers that have failed to respond to conventional therapies.[11]

Summary

Introduction

Delivered light dose (J/cm2) is the principal parameter guiding interstitial photodynamic therapy (I-PDT) of refractory locally advanced cancer. The aim of this study was to investigate the impact of light dose rate (irradiance, mW/cm2) and associated heating on tumour response and cure. METHODS: Finite-element modeling was used to compute intratumoural irradiance and dose to guide Photofrin® I-PDT in locally advanced SCCVII in C3H mice and large VX2 neck tumours in New Zealand White rabbits. RESULTS: In the mouse model, cure rates of 70–90% were obtained with I-PDT using 8.4–245 mW/cm[2] and ≥45 J/cm[2] in 100% of the SCCVII tumour. CONCLUSION: In Photofrin®-mediated I-PDT, a selected range of irradiance prompts effective photoreaction with tissue heating in the treatment of locally advanced mouse tumour. These irradiances were translated for effective local control of large VX2 tumours. Combination chemotherapy yields objective response rates of 10–36%.2 Re-irradiation is associated with significant toxicity.[3,4,5,6] Salvage surgery is associated with prolonged hospitalisation, and the cure rates are poor.[7,8] The newest immunotherapy regimens result in 5–16% overall response.[9,10]

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