Significance: India has one of the highest rates of oral cancer incidence in the world, accounting for 30% of reported cancers. In rural areas, a lack of adequate medical infrastructure contributes to unchecked disease progression and dismal mortality rates. Photodynamic therapy (PDT) has emerged as an effective modality with potential for treating early stage disease in resource-limited settings, while photosensitizer fluorescence can be leveraged for treatment guidance.
Aim: Our aim was to assess the capability of a simple smartphone-based device for imaging 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence for treatment guidance and monitoring as part of an ongoing clinical study evaluating low-cost technology for ALA-based PDT treatment of early oral cancer.
Approach: A total of 29 subjects with <2 cm diameter moderately/well-differentiated microinvasive ( < 5 mm depth) oral squamous cell carcinoma lesions (33 lesions total, mean area ∼1.23 cm2) were administered 60 mg / kg ALA in oral solution and imaged before and after delivery of 100 J / cm2 total light dose to the lesion surface. Smartphone-based fluorescence and white light (WL) images were analyzed and compared with ultrasound (US) imaging of the same lesions.
Results: We present a comparative analysis of pre- and post-treatment fluorescence, WL, and US images of oral lesions. There was no significant difference in the distribution of lesion widths measured by fluorescence and US (mean widths of 14.5 and 15.3 mm, respectively) and linear regression shows good agreement (R2 = 0.91). In general, PpIX fluorescence images obtained prior to therapeutic light delivery are able to resolve lesion margins while dramatic photobleaching (∼42 % ) is visible post-treatment. Segmentation of the photobleached area confirms the boundaries of the irradiated zone.
Conclusions: A simple smartphone-based approach for imaging oral lesions is shown to agree in most cases with US, suggesting that this approach may be a useful tool to aid in PDT treatment guidance and monitoring photobleaching as part of a low-cost platform for intraoral PDT.
Oral cancers are the 8th most common cancer among males. In India, this corresponds to almost 80,000 new cases per year. With such a disease burden, oral cancers are a prime cause of morbidity and functional disability.
Conventional treatment for oral cancers is surgery and radiation therapy which are fraught with physical and functional side effects, and the high cost and infrastructure requirements present barriers to timely intervention for patients in rural and/or resource-limited areas. Motivated by these considerations we sought to evaluate photodynamic therapy (PDT) as an approach which is inherently conducive to adaptation for resource-limited settings and has previously shown promising clinical results for early stage oral lesions. In this study we evaluate a low-cost platform for aminolevulinic acid (ALA)-based PDT consisting of a portable 635nm fiber-coupled LED light source integrated with 3D printed applicators for stable intraoral light delivery and smartphone-based fluorescence imaging for treatment guidance.
Using this technology, we treated 18 subjects with histologically confirmed T1N0M0 lesions of the buccal mucosa with a mean diameter of 1.38 cm2 and micro-invasive (≤ 5mm depth) disease. A total light dose of 100 J/cm2 was delivered in 3 to 5 fractions to the buccal mucosa after oral administration of 60mg/kg ALA (in 3 aliquots of 20mg/kg). The post-PDT investigations showed a 72% success rate (no residual malignancy in follow-up biopsy).
The treatment was very well tolerated and has potential for broader dissemination into primary care sites and as an early intervention for pre-malignant conditions including submucous fibrosis and leucoplakia.
Oral cancers are among the most prevalent malignancies in males. In developing countries like India where chewing tobacco and other carcinogen containing mixtures is common, incidence of oral cancers is high. Photodynamic therapy is emerging as a promising method for non-disfiguring treatment for early malignant lesions of the buccal mucosa with relatively few effects and potential for implementation in settings with limited medical infrastructure
We evaluate ultrasonography as an approach for assessment of PDT response in oral malignancies.In our study we selected stage 1 malignancy of the buccal mucosa using both ultrasonography followed by histopathology.The criterion for selection on USG was lesion length of 2cm or less and depth of 5mm confirmed by biopsy and histopathology analysis. Subsequently, the patients found positive on biopsy were treated with ALA PDT with a LED light source. Following treatment these patients were reassessed with ultrasound at day 10. The images obtained were compared and evaluated for change in the size of the lesion, their echopattern, vascularity, mucosal status etc.
It was found, lesions completely hypoechoic signifying necrosis came out negative on biopsy every single time, confirming hypoechogenecity as the single best indicator for success of PDT treatment. However, those lesions which did not develop necrosis but were negative on biopsy, the indirect markers were small initial size of the lesion, a lack of vascularity within the lesion and surrounding inflammation.
To conclude, ultrasonography is a convenient, reliable and radiation free method for post PDT evaluation of lesions of buccal mucosa.
India has one of the highest rates of oral cancer incidence in the world, with an estimated 80,000 new cases per year, accounting for 30% of reported cancers. In rural areas, a lack of adequate medical infrastructure contributes to unchecked disease progression and dismal mortality rates. PDT emerges as a potential modality which can be implemented in resource limited settings, while photosensitizer fluorescence can be leveraged for treatment guidance. Here, as part of an ongoing clinical study evaluating low-cost technology for ALA PDT treatment, we evaluated the capability of a simple smartphone-based device for imaging ALA-induced PpIX fluorescence. The imaging device itself consists of an annulus of 405nm LEDs for PpIX excitation with emission filter in the center mounted over the phone camera. 18 subjects having <2 cm diameter (mean size; ~1.38 cm2) lesions with micro-invasive (≤5 mm. depth) moderately/well-differentiated squamous cell carcinoma were administered 60 mg/kg ALA in oral solution and imaged before and after delivery of 100 J/cm2 total light dose to the lesion surface. We will present comparative analysis of pre-and post-treatment fluorescence, white light, and ultrasound images. In general, PpIX fluorescence images obtained prior to therapeutic light delivery are able to resolve lesion margins while dramatic photobleaching in post-treatment images confirms the irradiated zone. Overall this approach is able to generate sufficient fluorescence contrast for treatment guidance and monitoring photobleaching while the use of a smartphone-based device provides a low-cost, widely available platform with potential for telemedicine integration.
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