PEDSY
A complete dosimetry solution for Intracavitary PDT
Simphotek, together with its collaborator the Hospital of the University of Pennsylvania (Penn), is developing a new integrated PDT Explicit Dosimetry System and light delivery platform for quantitative measurement – PEDSy. It will be a novel, patent-pending hardware-software medical device, which will be optimized and rigorously validated under clinically-relevant conditions to deliver Intracavitary PDT to treat lung cancer and other indications. The product includes two key components:
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hardware for in situ PDT dosimetry and light source tracking in real-time (Penn),
software/hardware device (Simphotek Medical Devices) for treatment monitoring of incident light distribution throughout the pleural cavity as well as fluorescence from the photosensitizer (PS).
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The in situ hardware (Penn) is composed of a multi-channel instrument that can be used in the clinic during intracavitary PDT to measure not only conventional light dose but also the promising experimental PDT dose using the explicit dosimetry of light fluence rate and photosensitizer (PS) concentration. An IR navigation system and a 3D scanner will be developed to track the light source position in real-time as well as determining the geometrical shape of pleural surface for intracavitary PDT treatment in real-time. The Simphotek Medical Devices software will be an extended version of Dosieâ„¢ for light fluence rate distribution on the entire pleural cavity coupled with estimation of the PDT dose distribution along the pleural cavity.
Why PEDSy?
The prognosis for lung/mesothelioma cancer is very poor with a median survival of 12-18 months. Recent Phase 2 clinical trials by Penn doubled the median overall survival to 3 years for all 73 patients (100%) vs the standard of care of 1 -1.5 years. (Lancet 2016;387:1405). In addition, for patients without lymph node metastases, PDT increased the median overall survival by nearly five times to 7.3 years. This is a major breakthrough by the members of our Scientific Advisory Board Drs. Cengel, Zhu, and Busch. The focus of much of the history of PDT dosimetry has been the quantification of light dose as the main treatment outcome predictor. Our collaborators are turning things around: the preclinical data revealed that it is PDT dose that delivers a better quantifier for the treatment outcome.
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PEDSy will provide the necessary hardware and software support to estimate light fluence as well as light-drug concentration that will guarantee the delivery of a prescribed amount of light dose and PDT dose to the patients.
Animal studies validate that the PDT efficacy can be further improved by at least a factor of 2-4 over the light dose when the effects of the PS are included. The trick is to deliver evenly distributed light dose and PDT dose to the patient's target area. And this is what the final PEDSy product will do, thus, enabling the increasing overall survival by more than 2-5 times as recently observed by intracavitary PDT Phase 2 clinical trials in lung by Penn.
How PEDSy does it?
The PEDSy hardware will consist of several isotropic detectors connected to a multi-channel dosimetry system and the corresponding number of spectrometers capable of registering fluorescence light generated by the activated light drug, a.k.a. the photosensitizer (PS). The optical properties and fluorescence spectra at each location of measurement will be determined independently with a surface contact probe. The PEDSy hardware will be used to estimate light strength (as well as the light dose) and PS concentration in real-time. The measured tissue optical properties at the same sites will be taken into account in obtaining accurate PS concentration. Both cumulative and instantaneous PDT dose vs. time can be calculated using the estimated PS concentrations and known photochemical parameters.
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Current Dosie will be extended to support calculations of PDT dose for cumulative and instantaneous time over the entire treatment area. In ongoing clinical trials, PEDSy hardware measurements will be included in each of the chosen locations on the pleural surfaces that are currently measured by isotropic detectors for light dose during PDT. An integrated PDT laser source tracking system composed of a laser source and a 3D surface scanner will be developed to:
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reconstruct the pleural surface during PDT,
track and record the movement of the treatment laser wand positions,
display the PDT dose (fed by the PEDSy calculation device) in real-time, and
include detector locations, thereby providing guidance to the surgeon in order to ensure homogeneity in PDT dose.
Critical modules
PEDSy hardware
A limited working prototype of the PEDSy hardware is shown here (light delivery and tracking part is not shown). The light dose, PS concentrations, and tissue optical properties are monitored at chosen locations.
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(a) shows the enclosed prototype instrument;
(b) cut-out display of components, and
(c) a schematic diagram of the device.
PEDSy software
PEDSy simulation device will be an extension of Dosieâ„¢ that will support not only intracavitary PDT treatment planning but also treatment monitoring and treatment adjustment in real-time. It will collect the measurements from PEDSy hardware from several key sites and extrapolate the values throughout the cavity to estimate light dose and PDT-dose. Light powers and locations will be adjusted based on the calculations.
An example of light simulation for a sample lung using Dosie™, which will be incorporated into PEDSy software. The 3D fluence rate (intensity) map with the point light source location (white dot) is in the upper left corner, while other views show three 2D slices of the map – sagittal, coronal, and transverse views. The views are interactive which enables the user to inspect every detail in real time.
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A commercial version of PEDSy is under development, subject to final funding.
Meso at Penn
Meso is a difficult disease to treat where the lung is often sacrificed. However, our collaborators at Penn developed a lung saving technique in which the lung is pushed aside before PDT begins. During surgery a few light detectors are sutured into the lung cavity wall. A light wand system is used to translate the light over the light detectors sewed into the tissue.