Platform for ergonomic intraoral photodynamic therapy using low-cost, modular 3D-printed components: Design, comfort and clinical evaluation

Abstract

Oral cancer prevalence is increasing at an alarming rate worldwide, especially in developing countries which lack the medical infrastructure to manage it. For example, the oral cancer burden in India has been identified as a public health crisis. The high expense and logistical barriers to obtaining treatment with surgery, radiotherapy and chemotherapy often result in progression to unmanageable late stage disease with high morbidity. Even when curative, these approaches can be cosmetically and functionally disfiguring with extensive side effects. An alternate effective therapy for oral cancer is a light based spatially-targeted cytotoxic therapy called photodynamic therapy (PDT). Despite excellent healing of the oral mucosa in PDT, a lack of robust enabling technology for intraoral light delivery has limited its broader implementation. Leveraging advances in 3D printing, we have developed an intraoral light delivery system consisting of modular 3D printed light applicators with pre-calibrated dosimetry and mouth props that can be utilized to perform PDT in conscious subjects without the need of extensive infrastructure or manual positioning of an optical fiber. To evaluate the stability of the light applicators, we utilized an endoscope in lieu of the optical fiber to monitor motion in the fiducial markers. Here we showcase the stability (less than 2 mm deviation in both horizontal and vertical axis) and ergonomics of our applicators in delivering light precisely to the target location in ten healthy volunteers. We also demonstrate in five subjects with T1N0M0 oral lesions that our applicators coupled with a low-cost fiber coupled LED-based light source served as a complete platform for intraoral light delivery achieving complete tumor response with no residual disease at initial histopathology follow up in these patients. Overall, our approach potentiates PDT as a viable therapeutic option for early stage oral lesions that can be delivered in low resource settings.

Figure 1

(A) 3D Schematics and photograph of the applicators for three different regions in the mouth Anterior buccal cheek position, posterior buccal cheek position and retromolar region. The photographs showcase the integrated unit with the applicator (1), the bite wing (2) and the endoscope (3) utilized in the ergonomics clinical study. For photodynamic therapy in patients, we replaced the endoscope with a fiber that delivered 635 light from our custom designed light source. (B) Photograph of the oral cavity with ink marks in three points tested in the ergonomics study.

Figure 2

Flow chart of video and image processing method to calculate centroid of the fiducial ink mark mimicking the anterior buccal cheek, posterior buccal cheek or retromolar position imaged with a USB Endoscope fitted to the oral applicators.

Figure 3

Graphical representation of the scores given by the subjects post 10 minute testing of the applicators.

Figure 4

(A–C) Location of the fiducial ink mark centroid obtained from the post-processing of all the video frames from the 10 subjects. The horizontal (D–F) and vertical displacements (G–I) for the anterior buccal cheek position (left panel), posterior buccal cheek position (center panel) and the retromolar position (right panel) for the 10 subjects displayed as boxplots with mean of the centroid location in the 10 minute video, 25–75% percentile bars and outliers (black circles) that occur during any swallowing or other oral cavity motion.

Figure 5

(A) Pretreatment regular white light photograph of the lesion (outlined in black dotted line). (B,C)Fluorescence image of the PpIX accumulation (pre light irradiation) and photobleaching in the lesion region post irradiation. (D–E) Histology images of the biopsy taken before and after the treatment showcase absence of malignant cells post therapy.