Revisiting photodynamic therapy dosimetry: reductionist & surrogate approaches to facilitate clinical success
Autor: | Edward V. Maytin, Jonathan T. Elliott, Kimberley S. Samkoe, Scott C. Davis, Stephen P. Pereira, Tayyaba Hasan, Stephen C. Kanick, Brian W. Pogue |
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Rok vydání: | 2016 |
Předmět: |
medicine.medical_specialty
medicine.medical_treatment Photodynamic therapy Radiation Dosage Multimodal Imaging 01 natural sciences Clinical success 010309 optics 03 medical and health sciences 0302 clinical medicine 0103 physical sciences medicine Dosimetry Radiology Nuclear Medicine and imaging Medical physics Time sensitive Photosensitizing Agents Radiological and Ultrasound Technology Surrogate endpoint business.industry Photochemotherapy Treatment delivery 030220 oncology & carcinogenesis Treatment procedure Skin lesion business |
Zdroj: | Physics in Medicine and Biology. 61:R57-R89 |
ISSN: | 1361-6560 0031-9155 |
Popis: | Photodynamic therapy (PDT) can be a highly complex treatment, with many parameters influencing treatment efficacy. The extent to which dosimetry is used to monitor and standardize treatment delivery varies widely, ranging from measurement of a single surrogate marker to comprehensive approaches that aim to measure or estimate as many relevant parameters as possible. Today, most clinical PDT treatments are still administered with little more than application of a prescribed drug dose and timed light delivery, and thus the role of patient-specific dosimetry has not reached widespread clinical adoption. This disconnect is at least partly due to the inherent conflict between the need to measure and understand multiple parameters in vivo in order to optimize treatment, and the need for expedience in the clinic and in the regulatory and commercialization process. Thus, a methodical approach to selecting primary dosimetry metrics is required at each stage of translation of a treatment procedure, moving from complex measurements to understand PDT mechanisms in pre-clinical and early phase I trials, towards the identification and application of essential dose-limiting and/or surrogate measurements in phase II/III trials. If successful, identifying the essential and/or reliable surrogate dosimetry measurements should help facilitate increased adoption of clinical PDT. In this paper, examples of essential dosimetry points and surrogate dosimetry tools that may be implemented in phase II/III trials are discussed. For example, the treatment efficacy as limited by light penetration in interstitial PDT may be predicted by the amount of contrast uptake in CT, and so this could be utilized as a surrogate dosimetry measurement to prescribe light doses based upon pre-treatment contrast. Success of clinical ALA-based skin lesion treatment is predicted almost uniquely by the explicit or implicit measurements of photosensitizer and photobleaching, yet the individualization of treatment based upon each patients measured bleaching needs to be attempted. In the case of ALA, lack of PpIX is more likely an indicator that alternative PpIX production methods must be implemented. Parsimonious dosimetry, using surrogate measurements that are clinically acceptable, might strategically help to advance PDT in a medical world that is increasingly cost and time sensitive. Careful attention to methodologies that can identify and advance the most critical dosimetric measurements, either direct or surrogate, are needed to ensure successful incorporation of PDT into niche clinical procedures. |
Databáze: | OpenAIRE |
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