Accurate dosimetry has been a theme throughout the development of PDT to achieve optimal, repeatable treatment delivery. This can be relatively straightforward, such as in surface illumination using topical photosensitizer, where the administered light and drug doses can be easily standardized. However, for “volumetric” treatments of, for example, solid tumors or for large-area intracavitary treatments, the complex geometries, the need for multiple light sources and the heterogeneity of tissue optical properties, photosensitizer uptake and oxygenation, require more complete and rigorous pre-treatment planning as well as real-time in situ measurements to correlate with outcomes.
Multiple dosimetry approaches have been developed, including a) calculating/measuring the light fluence distribution, photosensitizer uptake and/or oxygenation and combining these in an ”effective-dose” model, b) measuring/imaging photosensitizer photobleaching as surrogate metric, and c) directly or indirectly detecting the singlet oxygen generation. The status, advantages and limitations of each approach are considered, including clinical practicality and utility.
The underlying assumption has been that there is a direct correlation between the effective PDT dose and the resulting outcome and evidence supports this in many cases. However, in some cases the effective dose has been a poor indicator of outcome. This response variance for a given “dose” has limited wide clinical adoption of PDT, particularly in oncology.
One factor that has likely contributed to the response variance is secondary immune regulation induced by the inflammatory processes resulting from PDT. There is evidence in preclinical tumor models that this can be the dominant, and highly favorable, mechanism, both for the primary tumor outcome and to impact tumor progression and metastases. However, this “PhotoChemical Immune Stimulation (PCIS)” essentially decouples outcome from the PDT biophysical dose. Hence, PCIS dosimetry presents major new dosimetric challenge that will need to incorporate not only the biophysical parameters but also the photobiological and immunological factors.
Brian C Wilson, Princess Margaret Cancer Centre-University Health Network/University of Toronto, CA