Photodynamic Therapy With Topical Metatetrahydroxychlorin (Fosgel) Is Ineffective for the Treatment of Anal Intraepithelial Neoplasia, Grade III
*Department of Dermatology, daggerDepartment of Radiation Oncology, Center for Optical Diagnostics and Therapy, double daggerDepartment of Internal Medicine, section signDepartment of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands, ||Department of Internal Medicine, MCRZ, Rotterdam, The Netherlands, paragraph signDepartment of Infectious Diseases, Leiden University Medical Center, The Netherlands, #Department of Internal Medicine, Haaglanden MC, The Hague, The Netherlands.JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 10/2009; 52(1):141-3. DOI: 10.1097/QAI.0b013e3181b05f93
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ABSTRACT: In order to understand the mechanisms of photodynamic therapy (PDT) it is important to monitor parameters during illumination that yield information on deposited PDT dose. The aim of this study is to investigate the possibility of monitoring implicit parameters, such as photobleaching, in addition to monitoring explicit parameters (fluence (rate), oxygenation, photosensitizer concentration) directly or indirectly. These parameters are monitored during PDT without interrupting the therapeutic illumination. Rats were injected with 0.3 mg kg(-1) m-THPC. Sixteen hours after administration the abdominal muscle in rats was irradiated for 1,500 seconds using clinically relevant fluence rates of 50, 100, and 250 mW cm(-1) of diffuser length at 652 nm. In addition to the linear diffuser for delivering treatment light, isotropic fiber-optic probes and fiber-optic probes for differential path-length spectroscopy (DPS) were placed on both sides of the muscle to monitor tissue physiological parameters, fluence rate, and fluorescence. The m-THPC treatment groups show a decrease in fluence rate throughout PDT of 16%, 19%, and 27% for the 50, 100, and 250 mW cm(-1) groups, respectively. Both during and post-PDT differences in vascular response between treatment groups and animals within the same treatment group are observed. Furthermore we show fluence rate dependent bleaching of m-THPC up to a measured fluence rate of 100 mW cm(-1). The data presented in this study show the possibility of simultaneously monitoring fluence (rate), fluorescence, hemoglobin oxygen saturation, and blood volume during PDT without interruptions to the therapeutic illumination. Differences in saturation profiles between animals and treatment groups indicate differences in vascular response during illumination. Furthermore, the relationship between fluence rate and m-THPC fluorescence photobleaching is complex in an interstitial environment.
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ABSTRACT: The objective of this study was to develop an applicator for delivery of light and monitoring of photodynamic therapy (PDT) in the anal cavity for treatment of anal intraepithelial neoplasia grade III (AIN III), which can progress to invasive anal cancer. Forty-eight hours before treatment, patients participating in the study were injected with 0.03 (n=2) or 0.075 (n=2) mg kg(-1) m-THPC. For light delivery and monitoring of PDT, an applicator based on standard anoscopy equipment was developed which facilitates, in addition to a light treatment fiber, fiber optic probes to monitor blood saturation, blood volume, fluorescence and fluence (rate) at two different locations in situ. Patients were given a light dose of 10-17 J cm(-2) at a fluence rate of 45-50 mW cm(-2) based on in situ measured light treatment parameters. We demonstrate that the applicator does not influence the fluence rate profile of the light treatment fiber. Furthermore this study shows the possibility of monitoring blood saturation, blood volume, fluorescence and fluence (rate) during therapeutic illumination without changing the light treatment protocol.
Article: Photodynamic therapy for anal cancer[Show abstract] [Hide abstract]
ABSTRACT: Invasive anal cancers are generally successfully treated by combined chemotherapy with radiation therapy (XRT). For those patients who locally fail this intervention many are salvaged by surgery which generally results in permanent colostomy. We examined the treatment and outcome of Photofrin based photodynamic therapy (PDT) in a cohort of patients with anal cancer who failed locally despite chemo-radiation (N=6) and two patients with positive margins of resection after excision of small T(1) squamous cell anal cancers who refused further surgery or chemo-radiation. PDT consisted of outpatient infusion of Photofrin at 1.2mg/kg followed 48 h later by outpatient illumination. Red light (630 nm) illumination was delivered by a 5 cm diffusing fiber, treating transphincterally at 300 J/cm followed by microlens illumination at 200 J/cm(2) to the perianal tumor bed with 2 cm margin. All patients completed PDT without incident and all have maintained local control of disease in the anal region for the length of follow up (18-48 months). PDT may serve as a new means to salvage local failures and perhaps could be employed as a primary treatment modality in select patients with early stage of disease.
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