Minimal required PDT light dosimetry for nonmuscle invasive bladder cancer.

Lothar Lilge,Fynn Schwiegelshohn,Daniel Molehuis,Yiwen Xu,Jenny Wu,Wayne Embree,Michael Nesbit,Leonid Vesselov,Michael A S Jewett,Girish S Kulkarni,Arkady Mandel,Vaughn Betz,Angelica Manalac

doi:10.1117/1.jbo.25.6.068001

Abstract

.Significance: Photodynamic therapy (PDT) could become a treatment option for nonmuscle invasive bladder cancer when the current high morbidity rate associated with red light PDT and variable PDT dose can be overcome through a combination of intravesical instillation of the photosensitizer and the use of green light creating a steep PDT dose gradient.Aim: To determine how a high PDT selectivity can be maintained throughout the bladder wall considering other efficacy determining parameters, in particular, the average optical properties of the mucosal layer governing the fluence rate multiplication factor, as well as the bladder shape and the position of the emitter in relationship to the bladder wall.Approach: We present three irradiance monitoring systems and evaluate their ability to enable selective bladder PDT considering previously determined photodynamic threshold values for the bladder cancer, mucosa and urothelium in a preclinical model, and the photosensitizer’s specific uptake ratio. Monte Carlo-based light propagation simulations performed for six human bladders at the time of therapy for a range of tissue optical properties. The performance of one irradiance sensing device in a clinical phase 1B trial is presented to underline the impact of irradiance monitoring, and it is compared to the Monte Carlo-derived dose surface histogram.Results: Monte Carlo simulations showed that irradiance monitoring systems need to comprise at least three sensors. Light scattering inside the bladder void needs to be minimized to prevent increased heterogeneity of the irradiance. The dose surface histograms vary significantly depending on the bladder shape and bladder volume but are less dependent on tissue optical properties.Conclusions: We demonstrate the need for adequate irradiance monitoring independent of a photosensitizer’s specific uptake ratio.

Highlights

The management of nonmuscle invasive bladder cancer (NMIBC) remains controversial.[1]
A recent review by Kamat et al.[2] stated that the recurrence rate following Bacillus Calmette Guerin (BCG) immunotherapy is in the 33% to 42% range, with around 10% of patients progressing to higher stage disease muscle invasion during therapy
Individual irradiance sensors were constructed by heating a 0.2-mm-wide metal blade to 75°C, the plastic’s transition temperature, and pressing it 75 to 100 μm into the plastique optical fibers (POFs) at predetermined positions from the distal end of the fiber

Summary

Introduction

The management of nonmuscle invasive bladder cancer (NMIBC) remains controversial.[1] Variation in practice patterns is high, which contributes to the very high cost per case. Lilge et al.: Minimal required PDT light dosimetry for nonmuscle invasive bladder cancer face cystectomy with well-documented morbidity when intravesical therapy, usually Bacillus Calmette Guerin (BCG), fails to control recurrent disease. A recent review by Kamat et al.[2] stated that the recurrence rate following BCG immunotherapy is in the 33% to 42% range, with around 10% of patients progressing to higher stage disease muscle invasion during therapy. Recurrence patterns include patients who are unresponsive or intolerant to BCG.[2] Various approaches to prolong the recurrence-free interval and, in particular, reduce early recurrences have been investigated, such as intravesical chemotherapy.[3] benefits are limited, and it is widely recognized that there is an unmet need for other more effective treatments.[4]

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