Complete dosimetry and delivery solution for I-PDT
Simphotek intends to develop an advanced (patent-pending) clinical and operating room cancer treatment system – INTELLI – that combines light-based medical device hardware and (Trade Secret) software designed to be complete dosimetry, delivery, feedback and treatment planning solution for interstitial PDT (I-PDT).
INTELLI will designate specific locations of one or more laser coupled fibers and control the laser light to treat deeply seated tumors (more than 10 mm in thickness) by activating the photosensitizer (PS) with the light via optically transparent catheters. I-PDT for Head and Neck therapy uses multiple fibers as shown.
Two metrics will be used for the locations search and power control: light dose (a conventional metric that works in most of the cases and is good for treatment planning) and a NEW metric, PDT dose, which takes into consideration the variable PS concentration fluctuations.
INTELLI includes the following critical components needed to make I-PDT treatment repeatable:
near real-time finite element (FE) solver to accurately simulate light intensity distribution,
dedicated equipment and software for automatic real-time monitoring of the treatment light dose and PDT dose, and
near real-time photokinetics (PK) simulations to account for variable PS concentration and distribution within a tumor
Some of these features are included in the early prototypes of the system that have been tested in initial clinical trials. The main feature – PDT feedback and adjustment based on real-time PDT-dose monitoring – will be included in the completed system and tested in a new clinical trial.
Recent pre-clinical studies at Penn verify that PDT dose is a better predictor of treatment outcomes than total light dose alone, which can significantly improve survival rates of cancer patients. Compared to the sophisticated commercial computational planning tools that are available for ionizing radiation therapy, the existing I-PDT treatment planning tools are minimal and clinicians usually prescribe the same total light dose, for a particular type of PS, irrespective of tumor heterogeneity in local micro-environmental parameters such as PS concentration. INTELLI will include necessary hardware equipment that monitors changes in optical parameters such as light tissue absorption and light tissue scattering over the treatment time and changes to PS concentration. This will enable INTELLI to adjust the treatment, so that he correct PDT dose is evenly distributed within the tumor, making INTELLI the first commercial system that integrates near real-time light simulation with PS concentration and improves the efficacy of I-PDT.
How INTELLI does it?
The INTELLI hardware controls and delivers the treatment laser light to the designated locations within the tumor and periodically runs treatment light and fluorescent light measurements over multiple wavelengths to monitor current light dose and to estimate tissue optical properties and PS concentration at chosen locations.
The INTELLI software generates a treatment plan that will prescribe the laser powers and treatment locations based on the scanned patient's tumor geometry and an oncologist input. During the procedure, the software will collect the measurements from INTELLI hardware to periodically assess if the current PDT treatment parameters are good enough to reach prescribed light dose and PDT dose everywhere within the tumor and at the margins. If inadequate doses are detected, the software will repeat its optimization engine run to adjust the current light powers.
The entire I-PDT treatment is complex and involves imaging and comprehensive treatment planning (see Background) for PDT pipeline description). Within this pipeline, INTELLI is used (1) to determine light powers and fiber locations, optimized for each patient individually (before OR), (2) to deliver the treatment light and to monitor the light dose and PDT dose in OR, and (3) to adjust the treatment plan during procedure to reach prescribed light dose and PDT dose, evenly distributed within the tumor region.
INTELLI will support
Developing a fully automated, bench top, system designed to support the administration of I-PDT with a light wavelength between 350-1050 nm.
incorporating treatment planning and light delivery platform that will allow users to correlate treatment response in near real time with light dose, PS retention, and changes in optical properties
Developing a comprehensive commercial I-PDT system that could be used to support multi-center clinical studies in order to disseminate the treatment worldwide.
The product is portable and will accompany the medical personnel to the operating room and provide the necessary support.
The main INTELLI’s modules are
Light transport solver with either Finite Element Method or Monte Carlo
Integrated light transport solver with Photokinetics simulation to determine light dose and PDT dose
Hardware components for light delivery including lasers, optical fibers, and detectors
Hardware for fluorescence measurements, such as monochrometers, to assess PS retention and monitor PS photobleaching.
Computer software for optimization to adjust treatment planning based on real-time measurements.
Hardware/electronics and computer software to record and display fluence (light dose), fluence rate, and PDT dose
A critical piece of INTELLI is the delivery, recording, and display system. Our strategic partner RPCC has already developed an experimental prototype system. The light treatment system will be combined with spectrophotometers to measure the concentration of the PS using fluorescence. INTELLI records all inputs, makes comparisons to expected values, and re-calculates – if necessary – and makes the adjusts to the treatment.
For deeply seated tumors or tumors that are more than 10 mm in thickness, intra-tumor light delivery is required to activate the photosensitizer (PS). In I-PDT, one or more laser fibers are used for treating the target tumor and margins. Typically, cylindrical diffuser optical fibers are inserted into optically transparent catheters, which have been located into specific regions in the tumor and surrounding area. The number and location of the fibers are specified by the treating physician, subject to the treatment planning software as operated by medical technicians, and depend on tumor size, location, PS and light wavelength.
At the pre-treatment phase, a CT scan is taken of the patient to image the tumor and surrounding areas.
Using commercial software in the laboratory the 2D CT scans are arranged in a 3D model for further analysis.
Technical staff creates a 3D geometry of the tumor and the surrounding area, which is segmented and labeled to identify the tumor (red), jaw bone (green), Hyoid Bone (light green), jugular vein (blue), vertebra (yellow), and cartilage (purple).
A commercial instrument, Zenascope is used to determine the optical properties used for the fluence and fluence rate simulations.
Using the optical properties and the 3D labeled geometry, an estimate of the placement of the fibers in the tumor is determined with the help of support staff who calculates the light fluence throughout the tumor using commercially available software.
If the calculations show the light dose reaches pre-defined levels and the treating physician approves the placement, the fibers are inserted into the patient in the operating room. Then the prescribed light powers are applied to the designated locations to treat tumor in the operating room.