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Significance: Photodynamic therapy (PDT) is an established cancer treatment utilizing light-activated photosensitizers (PS). Effective treatment hinges on the PDT dose-dependent on PS concentration and light fluence-delivered over time. We introduce an innovative eight-channel PDT dose dosimetry system capable of concurrently measuring light fluence and PS concentration during treatment. Aim: We aim to develop and evaluate an eight-channel PDT dose dosimetry system for simultaneous measurement of light fluence and PS concentration. By addressing uncertainties due to tissue variations, the system enhances accurate PDT dosimetry for improved treatment outcomes. Approach: The study positions eight isotropic detectors strategically within the pleural cavity before PDT. These detectors are linked to bifurcated fibers, distributing signals to both a photodiode and a spectrometer. Calibration techniques are applied to counter tissue-related variations and improve measurement accuracy. The fluorescence signal is normalized using the measured light fluence, compensating for variations in tissue properties. Measurements were taken in 78 sites in the pleural cavities of 20 patients. Results: Observations reveal minimal Photofrin concentration variation during PDT at each site, juxtaposed with significant intra- and inter-patient heterogeneities. Across 78 treated sites in 20 patients, the average Photofrin concentration for all 78 sites is 4.98 µM, with a median concentration of 4.47 µM. The average PDT dose for all 78 sites is 493.17 µMJ/cm², with a median dose of 442.79 µMJ/cm². A significant variation in PDT doses is observed, with a maximum difference of 3.1 times among all sites within one patient and a maximum difference of 9.8 times across all patients. Conclusions: The introduced eight-channel PDT dose dosimetry system serves as a valuable real-time monitoring tool for light fluence and PS concentration during PDT. Its ability to mitigate uncertainties arising from tissue properties enhances dosimetry accuracy, thus optimizing treatment outcomes and bolstering the effectiveness of PDT in cancer therapy. [ABSTRACT FROM AUTHOR]

Preclinical studies show improved prediction of treatment outcome using [ROS] rx than light fluence rate or PDT dose. We demonstrate ROSED in a clinical setting. Explicit dosimetry of light fluence, photosensitizer concentration, and oxygen concentration is used to quantify the reactive oxygen species explicit dosimetry (ROSED) during Photofrin-mediated pleural PDT. Light fluence and photosensitizer concentration were measured by a customized multi-channel PDT dose dosimeter system. Diffuse correlation spectroscopy (DCS) contact probes were sutured to the pleural cavity wall after surgical resection of pleural mesothelioma tumor to monitor tissue blood flow (BFI) during intraoperative PDT treatment. Tissue oxygen concentration can be determined by utilizing tumor blood flow measured by DCS. Large inter- and intra-patient heterogeneities in [ROS] rx were observed although an identical light dose of 60 J/cm2 was prescribed to all patients. This study summarizes the current results of ROSED for a Phase II pleural PDT clinical trial. [ABSTRACT FROM AUTHOR]

Uniform light fluence distribution for patients undergoing photodynamic therapy (PDT) is critical to ensure predictable PDT outcomes. However, current practice when delivering intrapleural PDT uses a point source to deliver light that is monitored by seven isotropic detectors placed within the pleural cavity to assess its uniformity. We have developed a real‐time infrared (IR) tracking camera to follow the movement of the light point source and the surface contour of the treatment area. The calculated light fluence rates were matched with isotropic detectors using a two‐correction factor method and an empirical model that includes both direct and scattered light components. Our clinical trial demonstrated that we can successfully implement the IR navigation system in 75% (15/20) of the patients. Data were successfully analyzed in 80% (12/15) patients because detector locations were not available for three patients. We conclude that it is feasible to use an IR camera‐based system to track the motion of the light source during PDT and demonstrate its use to quantify the uniformity of light distribution, which deviated by a standard deviation of 18% from the prescribed light dose. The navigation system will fail when insufficient percentage of light source positions is obtained (<30%) during PDT. [ABSTRACT FROM AUTHOR]

Purpose. The purpose of this study was to compare the dose to heart, left anterior descending (LAD) artery and lung between proton and photon beam irradiation for left-sided early stage breast cancer. Material and methods. Ten women with early stage left-sided breast cancer were treated with breast conserving surgery and radiation. Whole breast radiation was delivered for actual treatment via a tangential technique with deep inspiration breath hold (DIBH) utilizing inverse planned intensity-modulated radiation therapy (IMRT). Each patient was replanned on an Institutional Review Board (IRB)-approved prospective study using en face proton beam radiation with both uniform scanning (US) and pencil beam scanning (PBS) techniques. Results. Both PBS (0.011 Gy) and US (0.009 Gy) proton plans resulted in a significantly lower mean heart dose compared to IMRT (1.612 Gy) (p < 0.05 for PBS vs. IMRT and US vs. IMRT). The Dmean, Dmin, Dmax, and D0.2cm3 of the LAD with either proton technique were significantly lower (p = 0.005) compared to IMRT. Both US and PBS reduced the mean dose to the lungs compared to IMRT. The coverage of the breast planning target volume was comparable between photon and proton plans. Conclusions. The dose to whole heart was relatively low in this study of patients treated under conditions of DIBH. However, proton beam radiation was associated with lower minimum, maximum, and dose to 0.2 cm3 of the LAD, which is the critical structure for late radiation therapy effects, compared to even the most optimized photon beam plan with DIBH and IMRT. [ABSTRACT FROM AUTHOR]

For interstitial photodynamic therapy (PDT), cylindrical diffusing fibers (CDFs) are often used to deliver light. This study examines the feasibility and accuracy of using CDFs to characterize the absorption (&mi;a) and reduced scattering (&mi;′s) coefficients of heterogeneous turbid media. Measurements were performed in tissue-simulating phantoms with &mi;a between 0.1 and 1 cm-1 and &mi;′s between 3 and 10 cm-1 with CDFs 2 to 4 cm in length. Optical properties were determined by fitting the measured light fluence rate profiles at a fixed distance from the CDF axis using a heterogeneous kernel model in which the cylindrical diffusing fiber is treated as a series of point sources. The resulting optical properties were compared with independent measurement using a point source method. In a homogenous medium, we are able to determine the absorption coefficient &mi;a using a value of &mi;′s determined a priori (uniform fit) or &mi;′s obtained by fitting (variable fit) with standard (maximum) deviations of 6% (18%) and 18% (44%), respectively. However, the CDF method is found to be insensitive to variations in &mi; ′ s, thus requiring a complementary method such as using a point source for determination of &mi;′s. The error for determining &mi;a decreases in very heterogeneous turbid media because of the local absorption extremes. The data acquisition time for obtaining the one-dimensional optical properties distribution is less than 8 s. This method can result in dramatically improved accuracy of light fluence rate calculation for CDFs for prostate PDT in vivo when the same model and geometry is used for forward calculations using the extrapolated tissue optical properties. [ABSTRACT FROM AUTHOR]