JONATHAN CELLI, UNIVERSITY OF MASSACHUSETTS BOSTON
Mortality from cancer is on the rise in low- and middle-income countries, and the need is urgent for requisite treatment modalities that are low-cost, portable, and versatile in clinical environments with limited resources. One technique that may help fill this need is photodynamic therapy (PDT), which uses tumor-localizing photosensitizing agents (photosensitizers) to deliver light to the target tissue, causing cancer cell death. Compelling clinical evidence for the safety and efficacy of PDT has been documented, but bringing wider access to cancer patients will require local regulatory agencies to expand their parameters for approval, and manufacturers to commercialize light-delivery hardware and photosensitizers at price points that will make them widely accessible in low- and middle-income countries.
Photodynamic therapy may help to mitigate the growing disparity in cancer mortality rates between developed and developing countries.
The World Health Organization has estimated that by 2030, approximately 75% of all annual cancer deaths will occur in low- and middle-income countries. The disparity in cancer outcomes between developed and developing countries is
attributable in part to a lack of access to cancer treatment and imaging technologies in areas with limited resources. Curative treatment for most solid tumors involves surgery, which requires the availability of appropriately trained surgeons and associated facilities and support staff. Radiation therapy requires even more staffing and equipment that is often beyond the reach of cash-strapped clinical environments.
PDT is FDA approved in the U.S. for the treatment of non-small-cell lung cancer, which is a catchall term for malignant cells that can occur in the lung tissue of both smokers and nonsmokers. PDT has also been approved to treat actinic keratosis, or scaly patches on the skin, for which the technique is used along with the photosensitizing precursor aminolevulinic acid (ALA). Since photosensitizers also serve as tumor-localizing fluorescence contrast agents, ALA photosensitization is also FDA approved for fluorescence-guided resection of malignant glioma. PDT is noted for being well tolerated, for having minimal side effects, and for its ability to induce cell death in otherwise therapeutically resistant tumors. Equally important, PDT is also inherently conducive to low-cost instrumentation. Visible photons are cheap to produce using LED light sources or low-cost laser diodes. Provided that light can be delivered minimally invasively without the need for complex intraoperative procedures, the entire process of photosensitization and light delivery can be streamlined for use as a simple nonsurgical intervention.
While working with collaborators at the Massachusetts General Hospital and clinical partners at Aligarh Muslim University in India, we have seen firsthand how PDT can be leveraged effectively in the field to treat early-stage oral cancers using a portable battery-powered LED light source developed specifically for this application. Our study was motivated by the public health crisis in India, where widespread use of chewing tobacco products is driving the highest rates of oral cancer incidence in the world. In preclinical studies we had already established that the cheap LED light source we had built produced similar results to those of a more traditional medical laser for PDT treatment. For our study, a simple smartphone-mounted fluorescence excitation LED array and an emission filter over the camera sensor were used to guide treatment. This hardware cost less than $800 to prototype, and it was judged user-friendly by clinicians who had no prior PDT experience. Using this device, we saw complete tumor response after a single PDT session in 22 out of the first 30 patients.
Despite such promising results, challenges to achieving widespread use of PDT remain. While hardware may be inexpensive to prototype in an academic lab, long-term sustainability requires industry to buy in and develop treatment protocols that work with the technology. Small, low-cost light sources need to be marketed at a price point that is accessible to primary care centers. These components must be marketed effectively enough that low-cost photosensitizers and light delivery systems are profitable to mass-produce. And, currently, 5-ALA is not an approved protocol in many low- and middle-income countries and it is too expensive for them, in any case.
Once these hurdles are overcome, PDT may help to mitigate the growing disparity in cancer mortality rates between developed and developing countries. And, ultimately, leveraging cloud-based technologies and telemedicine connectivity to guide remote clinicians virtually in the use of these therapeutic interventions will help place PDT in the hands of care providers in rural clinics that traditionally have been cut off from cutting-edge cancer treatment technologies.
Meet the author
Jonathan Celli, Ph.D., is an associate professor of physics at the University of Massachusetts Boston. He received a doctorate in physics from Boston University and postdoctoral training at the Wellman Center for Photomedicine at Massachusetts General Hospital; email: [email protected].
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