A Comparison of Dose Metrics to Predict Local Tumor Control for Photofrin-mediated Photodynamic Therapy.

This preclinical study examines light fluence, photodynamic therapy (PDT) dose and "apparent reacted singlet oxygen," [1 O2 ]rx , to predict local control rate (LCR) for Photofrin-mediated PDT of radiation-induced fibrosarcoma (RIF) tumors. Mice bearing RIF tumors were treated with in-air fluences (50-250 J cm-2 ) and in-air fluence rates (50-150 mW cm-2 ) at Photofrin dosages of 5 and 15 mg kg-1 and a drug-light interval of 24 h using a 630-nm, 1-cm-diameter collimated laser. A macroscopic model was used to calculate [1 O2 ]rx and PDT dose based on in vivo explicit dosimetry of the drug concentration, light fluence and tissue optical properties. PDT dose and [1 O2 ]rx were defined as a temporal integral of drug concentration and fluence rate, and singlet oxygen concentration consumed divided by the singlet oxygen lifetime, respectively. LCR was stratified for different dose metrics for 74 mice (66 + 8 control). Complete tumor control at 14 days was observed for [1 O2 ]rx ≥ 1.1 mm or PDT dose ≥1200 µm J cm-2 but cannot be predicted with fluence alone. LCR increases with increasing [1 O2 ]rx and PDT dose but is not well correlated with fluence. Comparing dosimetric quantities, [1 O2 ]rx outperformed both PDT dose and fluence in predicting tumor response and correlating with LCR.

Assessment of photodynamic therapy using porfimer sodium for esoph ageal, bladder and lung cancers

OBJECTIVES OF THE ASSESSMENT: The Ministère de la Santé et des Services sociaux (MSSS) asked the Agence d'évaluation des technologies et des modes d'intervention en santé (AETMIS) to evaluate the efficacy of photodynamic therapy using porfimer sodium for its approved oncological indications. This report reveals the results of the assessment, attempts to adequately situate this treatment within the therapeutic arsenal available in Québec, and presents some preliminary observations on its use for the treatment of Barrett's esophagus. METHODOLOGY: The literature search strategy we used located two reports produced by health-technology assessment agencies: the Comité d'évaluation et de diffusion des innovations technologiques (CEDIT), associated with the Assistance Publique-Hôpitaux de Paris in France (1999), and the Institute for Clinical Systems Improvement (ICSI) in the United States (1997 and 2002). To supplement this informa-tion, we searched MEDLINE for all relevant articles published between January 1997 and December 2003. Assessment of these studies was based on the scheme for grading scientific evidence proposed inthe Canadian Guide to Clinical Preventive Health Care. RESULTS: With respect to cancers of the lung and bladder and superficial esophageal cancers, findings seem to indicate that photodynamic therapy with Photofrin® (PDT­PF) does have a therapeutic effect but that there is insuffi-cient evidence to conclude that it has any advantage over other available treatments be used as a complementary treatment.Still, we will need to obtain stronger scientific evidence of the advantages of PDT over other treatments and to examine its impact on the Québec health-care system before its use can be justified for these new applications. RECOMMENDATIONS: In light of this analysis, AETMIS recommends the following: -For the treatment of lung and bladder cancers and superficial esophageal cancers, PDT (PF) should be used only for clinical research purposes and should not be au-thorized for public coverage; -For the palliative treatment of advanced esophageal cancer, PDT (PF) should be considered a possible option when recog-nized treatments are contraindicated and should undergo further clinical research; -For the treatment of Barrett's esophagus, PDT (PF) should be fully assessed before it is introduced into current practic; -A technology watch should be imple-mented to track technological advances in PDT in general and its new applications in particular.(AU)