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Bergein F Overholt - One of the best experts on this subject based on the ideXlab platform.
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Optimization of light dosimetry for photodynamic therapy of Barrett's esophagus
2016Co-Authors: Masoud Panjehpour, Bergein F Overholt, Mary N Phan, John M. HaydekAbstract:Background and Objective: Photodynamic therapy (PDT) may be used for ablation of high grade dysplasia and/or early cancer (HGD/T1) in Barrett's esophagus. A complication of PDT is esophageal stricture. The objective of this study was to find the lowest light dose to potentially reduce the incidence of strictures while effectively ablating HGDITI. Materials and Methods: Patients (n=1 13) with HGD/T1 received an intravenous injection of Porfimer sodium (2 mg/kg). Three days later, laser light (630 nm) was delivered using a cylindrical diffuser inserted in a 20 mm-diameter PDT balloon. Patients were treated at light doses of 1 1 5 J/cm, I 05 J/cm, 95 J/cm and 85 Jlcm. The efficacy was determined by four quadrant biopsies of the treated area three months after PDT. The formation of stricture was determined by the incidence of dysphagia and the need for esophageal dilation. Strictures were considered mild if they required less that 6 dilations, and severe if 6 or more dilations were required. Efficacy and incidence of strictures were tabulated as a funôtion of light dose. Results: Using I 15 J/cm, there were 17 % of patients with residual HGD/T1 after one treatment. However, when the light doses of I 05 J/cm, 95 J/cm and 85 J/cm were used, the residual HGD/T1 after one PDT session was increased to 33%, 30 % and 32%, respectively. The overall incidence of strictures (mild and severe) was not correlated to the light dose. However, the incidence of severe strictures was directly proportional to the light dose. Using the light dose of I I 5 J/cm, I 5.3 % of patients developed severe strictures compared to about 5 % in the groups of patients who received the lower light doses. Conclusions: Decreasing the light dose below I I 5 J/cm doubled the rate of residual HGD/T1 after one treatment while reducing the incidence of severe strictures to one-third of cases from I I 5 JIcm. The results may be used to evaluate the risks and benefits of different light doses
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squamous overgrowth is not a safety concern for photodynamic therapy for barrett s esophagus with high grade dysplasia
Gastroenterology, 2009Co-Authors: Mary P Bronner, Bergein F Overholt, Shari L Taylor, Rodger C Haggitt, Kenneth K Wang, Steven J Burdick, Charles J Lightdale, Michael B Kimmey, Hector R Nava, Michael V SivakAbstract:Background & Aims Photodynamic therapy with Porfimer sodium combined with acid suppression (PHOPDT) is used to treat patients with Barrett's esophagus (BE) with high-grade dysplasia (HGD). A 5-year phase 3 trial was conducted to determine the extent of squamous overgrowth of BE with HGD after PHOPDT. Methods Squamous overgrowth was compared in patients with BE with HGD randomly assigned (2:1) to receive PHOPDT (n = 138) or 20 mg omeprazole twice daily (n = 70). Patients underwent 4-quadrant jumbo esophageal biopsies every 2 cm throughout the pretreatment length of BE until 4 consecutive quarterly follow-up results were negative for HGD and then biannually up to 5 years or treatment failure. Endoscopies were reviewed by blinded gastroenterology pathologists. Results Histologic assessment of 33,658 biopsies showed no significant difference ( P > .05) in squamous overgrowth between groups when compared per patient (30% vs 33%) or per biopsy (0.5% vs 1.3%), or when the average number of biopsies with squamous overgrowth were compared per patient (0.48 vs 0.66). The highest grade of neoplasia per endoscopy was not found exclusively beneath squamous mucosa in any patient. Conclusions No difference was observed in squamous overgrowth between patients given PHOPDT plus omeprazole compared with only omeprazole. Squamous overgrowth did not obscure the most advanced neoplasia in any patient. Treatment of HGD with PHOPDT in patients with BE does not present a long-term risk of failure to detect subsquamous dysplasia or carcinoma.
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photodynamic therapy of barrett s esophagus ablation of barrett s mucosa and reduction in p53 protein expression after treatment
Anticancer Research, 2008Co-Authors: Masoud Panjehpour, Bergein F Overholt, Domenico Coppola, Tuan Vodinh, Suzanne OverholtAbstract:Background: The effectiveness of photodynamic therapy (PDT) for ablation of high grade dysplasia (HGD) in Barrett's esophagus (BE) is typically reported histologically. Following successful PDT, Barrett's mucosa is replaced with neosquamous mucosa. The objective of this study was to compare the expression of p53 protein in neosquamous mucosa as compared to that in HGD samples not treated with PDT. Patients and Methods: The patients were divided into two groups. Group I patients (n=12) had been treated with PDT for HGD and provided 23 biopsy samples of neosquamous mucosa. Group II patients (n=10) had not received any ablative therapies for BE and provided 14 HGD samples. The immunohistochemical (IHC) staining for p53 protein was performed using mouse anti-human monoclonal antibody DO-1. The degree of p53 protein expression in the cell nuclei was scored using an established IHC scoring system (0 for negative samples and range of 2 to 8 for positive samples). Results: The HGD samples showed diffuse strong p53 staining. The median IHC score for HGD was 7.0. The median IHC score for neosquamous mucosa following PDT was 4.0, with positive scores indicating weak staining in the basal layer of the neosquamous samples. There was significantly lower p53 expression in the neosquamous samples compared to that in the HGD samples (p<0.001). Conclusion: Significantly lower p53 protein expression was detected in neosquamous mucosa of patients who had received PDT for HGD, suggesting a decreased risk for neoplastic progression after treatment. Barrett's esophagus (BE) is a premalignant condition associated with chronic acid reflux. A diagnosis of BE with high grade dysplasia (HGD) places the patient in a high risk category for developing adenocarcinoma of the esophagus. Photodynamic therapy (PTD) using Porfimer sodium, is a new endoscopic technique for the ablation of HGD in BE (1, 2). Successful PDT treatment, in the presence of effective acid suppression therapy, results in ablation of Barrett's mucosa with replacement by squamous (neosquamous) mucosa over the treated area. Evaluation of the response to PDT is through an aggressive follow-up biopsy protocol with histological examination by an expert pathologist. The histological documentation of
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Porfimer sodium photodynamic therapy for management of barrett s esophagus with high grade dysplasia
Lasers in Surgery and Medicine, 2006Co-Authors: Masoud Panjehpour, Bergein F OverholtAbstract:Porfimer sodium photodynamic therapy (ps-PDT) for Barrett's esophagus is a powerful endoscopic treatment that can eliminate high-grade dysplasia (HGD) and Barrett's mucosa and reduce the risk of development of cancer in these patients. Ps-PDT typically results in destruction of Barrett's esophagus in the majority of the treated area. However, residual small island of Barrett's mucosa may persist after PDT. Therefore, adjuvant thermal ablation should be available during follow-up endoscopies for ablation of residual islands of Barrett's mucosa. PDT should be applied concurrent with effective proton pump inhibitor therapy. This article provides a practical guide for application of Porfimer sodium balloon PDT for management of Barrett's esophagus with HGD. Recommendations are provided for patient selection and screening, delivery of PDT to include light dosimetry, methodology for follow-up endoscopies, as well as discussing the potential side effects and complications.
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a 5 year randomized phase iii trial of efficacy and safety of photodynamic therapy using Porfimer sodium in high grade dysplasia in barrett s esophagus
Gastrointestinal Endoscopy, 2006Co-Authors: Bergein F Overholt, Kenneth K Wang, Steven J Burdick, Charles J Lightdale, Michael B Kimmey, Hector R Nava, Norman S Nishioka, Michael Sivak, Hugh Barr, Chad DavisAbstract:A 5-Year Randomized Phase III Trial of Efficacy and Safety of Photodynamic Therapy Using Porfimer Sodium in High-Grade Dysplasia in Barrett’s Esophagus Bergein Overholt, Kenneth Wang, Steven Burdick, Charles Lightdale, Michael Kimmey, Hector Nava, Michael Sivak, Norman Nishioka, Hugh Barr, Chad Davis, Norman Marcon, Marcos Pedrosa, Mary Bronner, Michelle Depot Purpose: Barrett’s esophagus (BE) with high-grade dysplasia (HGD) patients were enrolled in a two-year trial comparing photodynamic therapy (PDT) with Porfimer sodium (POR) plus 20 mg BID omeprazole (O) [PORPDT] with standard therapy of acid suppression with O [O alone] and followed for an additional 3 years. At 2 years, HGD ablation occurred in 77% of PORPDT patients versus 39% in O alone patients (p ! 0.0001). As HGD and possible cancer development in BE are inextricably linked, the trial was continued over 5 years to assess longer-term HGD ablation and cancer occurrence. Methods: Patients with BE and HGD were randomized (2:1) to PORPDT (n Z 138) or O alone (n Z 70). Patients on PDT received 2 mg/kg i.v. of POR followed by endoscopic laser light exposure of Barrett’s mucosa at a wavelength of 630 nm within 40-50 hours up to a maximum of 3 courses administered at least 90 days apart. Every 3 months, patients underwent 4-quadrant jumbo esophageal biopsies at 2-cm intervals. Pathologists based at one center assessed biopsies and were blinded to treatment assignment and patient identity. Results: At 5 years, PORPDT was significantly more effective than O alone in eliminating HGD (p ! 0.0001) and in preventing progression to cancer (p Z 0.027) with about twice the likelihood of cancer occurring in O alone (29%) compared to PORPDT (15%). HGD ablation at 5 years confirmed the significant difference found at 2 years (77% PORPDT, 39% O alone). Conclusions: This 5-year large randomized trial showed clearly that PORPDT is a statistically and clinically effective endoscopic therapy in eliminating HGD and in reducing the incidence of cancer in BE patients with HGD compared to O alone.
Thomas J. Dougherty - One of the best experts on this subject based on the ideXlab platform.
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A dose ranging study of photodynamic therapy with Porfimer sodium (Photofrin®) for treatment of basal cell carcinoma
Lasers in Surgery and Medicine, 2006Co-Authors: Allan R. Oseroff, Leslie R. Blumenson, John C. Parsons, Noreen P. Frawley, B. Dale Wilson, Michele T. Cooper, Thomas S Mang, David A Bellnier, Nathalie C Zeitouni, Thomas J. DoughertyAbstract:Background and Objectives While basal cell carcinoma (BCC) is effectively treated by several methods, many patients with numerous or frequently occurring lesions seek alternatives that can treat multiple cancers, with improved cosmetic outcome. PDT for esophageal and lung carcinomas is approved at a Porfimer sodium (Photofrin®) dose of 2 mg/kg, but lower doses increase selectivity and decrease both cutaneous phototoxicity and cost. We evaluated low doses of Porfimer sodium PDT for treatment of multiple BCC. Materials and Methods Seventy-seven patients with 2,041 BCC were injected with 0.75, 0.875, or 1.0 mg/kg Porfimer sodium and treated 2 days later with 630-nm light. Clinical responses were determined at 6 months, then periodically to 5 years. Results Increasing Porfimer sodium dose increased complete responses (CR), with initial CR rates of 72.7% (66–78%, 95% CI), 79.9% (73–86%, 95% CI), and 92.2% (91–93%, 95% CI), albeit with some lower selectivity at the highest dose. At 1 mg/kg, 5-year recurrence rates were 28% (21–35%, 95% CI) and 15% (11–18%, 95% CI) for sporadic and nevoid basal cell carcinoma syndrome (NBCCS) lesions, respectively. Conclusions This is the largest dose-ranging study of Porfimer sodium, and the largest number of lesions treated in a single study. We found that with 1 mg/kg Porfimer sodium, PDT can be a selective and durable treatment for sporadic and NBCCS-associated BCC. Lasers Surg. Med. 38:417–426, 2006. © 2006 Wiley-Liss, Inc.
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clinical pharmacokinetics of the pdt photosensitizers Porfimer sodium photofrin 2 1 hexyloxyethyl 2 devinyl pyropheophorbide a photochlor and 5 ala induced protoporphyrin ix
Lasers in Surgery and Medicine, 2006Co-Authors: David A Bellnier, Allan R. Oseroff, Hector R Nava, William R Greco, Gregory M Loewen, Thomas J. DoughertyAbstract:Background and Objectives Photodynamic therapy (PDT) uses a photosensitizer activated by light, in an oxygen-rich environment, to destroy malignant tumors. Clinical trials of PDT at Roswell Park Cancer Institute (RPCI) use the photosensitizers Photofrin, Photochlor, and 5-ALA-induced protoporphyrin IX (PpIX). In some studies the concentrations of photosensitizer in blood, and occasionally in tumor tissue, were obtained. Pharmacokinetic (PK) data from these individual studies were pooled and analyzed. This is the first published review to compare head-to-head the PK of Photofrin and Photochlor. Study Design/Materials and Methods Blood and tissue specimens were obtained from patients undergoing PDT at RPCI. Concentrations of Photofrin, Photochlor, and PpIX were measured using fluorescence analysis. A non-linear mixed effects modeling approach was used to analyze the PK data for Photochlor (up to 4 days post-infusion; two-compartment model) and a simpler multipatient-data-pooling approach was used to model PK data for both Photofrin and Photochlor (at least 150 days post-infusion; three-compartment models). Physiological parameters were standardized to correspond to a standard (70 kg; 1.818 m2 surface area) man to facilitate comparisons between Photofrin and Photochlor. Results Serum concentration-time profiles obtained for Photofrin and Photochlor showed long circulating half-lives, where both sensitizers could be found more than 3 months after intravenous infusion; however, estimated plasma clearances (standard man) were markedly smaller for Photofrin (25.8 ml/hour) than for Photochlor (84.2 ml/hour). Volumes of distribution of the central compartment (standard man) for both Photofrin and Photochlor were about the size (3.14 L, 4.29 L, respectively) of plasma volume, implying that both photosensitizers are almost 100% bound to serum components. Circulating levels of PpIX were generally quite low, falling below the level of instrument sensitivity within a few days after topical application of 5-ALA. Conclusion We have modeled the PK of Photochlor and Photofrin. PK parameter estimates may, in part, explain the relatively long skin photosensitivity attributed to Photofrin but not Photochlor. Due to the potential impact and limited experimental PK data in the PDT field further clinical studies of photosensitizer kinetics in tumor and normal tissues are warranted. Lasers Surg. Med. © 2006 Wiley-Liss, Inc.
Hector R Nava - One of the best experts on this subject based on the ideXlab platform.
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squamous overgrowth is not a safety concern for photodynamic therapy for barrett s esophagus with high grade dysplasia
Gastroenterology, 2009Co-Authors: Mary P Bronner, Bergein F Overholt, Shari L Taylor, Rodger C Haggitt, Kenneth K Wang, Steven J Burdick, Charles J Lightdale, Michael B Kimmey, Hector R Nava, Michael V SivakAbstract:Background & Aims Photodynamic therapy with Porfimer sodium combined with acid suppression (PHOPDT) is used to treat patients with Barrett's esophagus (BE) with high-grade dysplasia (HGD). A 5-year phase 3 trial was conducted to determine the extent of squamous overgrowth of BE with HGD after PHOPDT. Methods Squamous overgrowth was compared in patients with BE with HGD randomly assigned (2:1) to receive PHOPDT (n = 138) or 20 mg omeprazole twice daily (n = 70). Patients underwent 4-quadrant jumbo esophageal biopsies every 2 cm throughout the pretreatment length of BE until 4 consecutive quarterly follow-up results were negative for HGD and then biannually up to 5 years or treatment failure. Endoscopies were reviewed by blinded gastroenterology pathologists. Results Histologic assessment of 33,658 biopsies showed no significant difference ( P > .05) in squamous overgrowth between groups when compared per patient (30% vs 33%) or per biopsy (0.5% vs 1.3%), or when the average number of biopsies with squamous overgrowth were compared per patient (0.48 vs 0.66). The highest grade of neoplasia per endoscopy was not found exclusively beneath squamous mucosa in any patient. Conclusions No difference was observed in squamous overgrowth between patients given PHOPDT plus omeprazole compared with only omeprazole. Squamous overgrowth did not obscure the most advanced neoplasia in any patient. Treatment of HGD with PHOPDT in patients with BE does not present a long-term risk of failure to detect subsquamous dysplasia or carcinoma.
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clinical pharmacokinetics of the pdt photosensitizers Porfimer sodium photofrin 2 1 hexyloxyethyl 2 devinyl pyropheophorbide a photochlor and 5 ala induced protoporphyrin ix
Lasers in Surgery and Medicine, 2006Co-Authors: David A Bellnier, Allan R. Oseroff, Hector R Nava, William R Greco, Gregory M Loewen, Thomas J. DoughertyAbstract:Background and Objectives Photodynamic therapy (PDT) uses a photosensitizer activated by light, in an oxygen-rich environment, to destroy malignant tumors. Clinical trials of PDT at Roswell Park Cancer Institute (RPCI) use the photosensitizers Photofrin, Photochlor, and 5-ALA-induced protoporphyrin IX (PpIX). In some studies the concentrations of photosensitizer in blood, and occasionally in tumor tissue, were obtained. Pharmacokinetic (PK) data from these individual studies were pooled and analyzed. This is the first published review to compare head-to-head the PK of Photofrin and Photochlor. Study Design/Materials and Methods Blood and tissue specimens were obtained from patients undergoing PDT at RPCI. Concentrations of Photofrin, Photochlor, and PpIX were measured using fluorescence analysis. A non-linear mixed effects modeling approach was used to analyze the PK data for Photochlor (up to 4 days post-infusion; two-compartment model) and a simpler multipatient-data-pooling approach was used to model PK data for both Photofrin and Photochlor (at least 150 days post-infusion; three-compartment models). Physiological parameters were standardized to correspond to a standard (70 kg; 1.818 m2 surface area) man to facilitate comparisons between Photofrin and Photochlor. Results Serum concentration-time profiles obtained for Photofrin and Photochlor showed long circulating half-lives, where both sensitizers could be found more than 3 months after intravenous infusion; however, estimated plasma clearances (standard man) were markedly smaller for Photofrin (25.8 ml/hour) than for Photochlor (84.2 ml/hour). Volumes of distribution of the central compartment (standard man) for both Photofrin and Photochlor were about the size (3.14 L, 4.29 L, respectively) of plasma volume, implying that both photosensitizers are almost 100% bound to serum components. Circulating levels of PpIX were generally quite low, falling below the level of instrument sensitivity within a few days after topical application of 5-ALA. Conclusion We have modeled the PK of Photochlor and Photofrin. PK parameter estimates may, in part, explain the relatively long skin photosensitivity attributed to Photofrin but not Photochlor. Due to the potential impact and limited experimental PK data in the PDT field further clinical studies of photosensitizer kinetics in tumor and normal tissues are warranted. Lasers Surg. Med. © 2006 Wiley-Liss, Inc.
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a 5 year randomized phase iii trial of efficacy and safety of photodynamic therapy using Porfimer sodium in high grade dysplasia in barrett s esophagus
Gastrointestinal Endoscopy, 2006Co-Authors: Bergein F Overholt, Kenneth K Wang, Steven J Burdick, Charles J Lightdale, Michael B Kimmey, Hector R Nava, Norman S Nishioka, Michael Sivak, Hugh Barr, Chad DavisAbstract:A 5-Year Randomized Phase III Trial of Efficacy and Safety of Photodynamic Therapy Using Porfimer Sodium in High-Grade Dysplasia in Barrett’s Esophagus Bergein Overholt, Kenneth Wang, Steven Burdick, Charles Lightdale, Michael Kimmey, Hector Nava, Michael Sivak, Norman Nishioka, Hugh Barr, Chad Davis, Norman Marcon, Marcos Pedrosa, Mary Bronner, Michelle Depot Purpose: Barrett’s esophagus (BE) with high-grade dysplasia (HGD) patients were enrolled in a two-year trial comparing photodynamic therapy (PDT) with Porfimer sodium (POR) plus 20 mg BID omeprazole (O) [PORPDT] with standard therapy of acid suppression with O [O alone] and followed for an additional 3 years. At 2 years, HGD ablation occurred in 77% of PORPDT patients versus 39% in O alone patients (p ! 0.0001). As HGD and possible cancer development in BE are inextricably linked, the trial was continued over 5 years to assess longer-term HGD ablation and cancer occurrence. Methods: Patients with BE and HGD were randomized (2:1) to PORPDT (n Z 138) or O alone (n Z 70). Patients on PDT received 2 mg/kg i.v. of POR followed by endoscopic laser light exposure of Barrett’s mucosa at a wavelength of 630 nm within 40-50 hours up to a maximum of 3 courses administered at least 90 days apart. Every 3 months, patients underwent 4-quadrant jumbo esophageal biopsies at 2-cm intervals. Pathologists based at one center assessed biopsies and were blinded to treatment assignment and patient identity. Results: At 5 years, PORPDT was significantly more effective than O alone in eliminating HGD (p ! 0.0001) and in preventing progression to cancer (p Z 0.027) with about twice the likelihood of cancer occurring in O alone (29%) compared to PORPDT (15%). HGD ablation at 5 years confirmed the significant difference found at 2 years (77% PORPDT, 39% O alone). Conclusions: This 5-year large randomized trial showed clearly that PORPDT is a statistically and clinically effective endoscopic therapy in eliminating HGD and in reducing the incidence of cancer in BE patients with HGD compared to O alone.
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photodynamic therapy with Porfimer sodium versus thermal ablation therapy with nd yag laser for palliation of esophageal cancer a multicenter randomized trial
Gastrointestinal Endoscopy, 1995Co-Authors: Charles J Lightdale, Bergein F Overholt, Stephen K Heier, Norman E Marcon, James S Mccaughan, Hans Gerdes, Michael Sivak, Gregory V Stiegmann, Hector R NavaAbstract:Abstract Background: Photodynamic therapy (PDT) is a different type of laser treatment from Nd:YAG thermal ablation for palliation of dysphagia from esophageal cancer. Methods: In this prospective, multicenter study, patients with advanced esophageal cancer were randomized to receive PDT with Porfimer sodium and argon-pumped dye laser or Nd:YAG laser therapy. Results: Two hundred thirty-six patients were randomized and 218 treated (PDT 110, Nd:YAG 108) at 24 centers. Improvement in dysphagia was equivalent between the two treatment groups. Objective tumor response was also equivalent at week 1, but at month 1 was 32% after PDT and 20% after Nd:YAG ( p More mild to moderate complications followed PDT, including sunburn in 19% of patients. Perforations from laser treatments or associated dilations occurred after PDT in 1%, Nd:YAG 7% ( p p Conclusions: Photodynamic therapy with Porfimer sodium has overall equal efficacy to Nd:YAG laser thermal ablation for palliation of dysphagia in esophageal cancer, and equal or better objective tumor response rate. Temporary photosensitivity is a limitation, but PDT is carried out with greater ease and is associated with fewer acute perforations than Nd:YAG laser therapy. (Gastrointest Endosc 1995;42:507-12.)
Thomas S Mang - One of the best experts on this subject based on the ideXlab platform.
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the use of photodynamic therapy using 630nm laser light and Porfimer sodium for the treatment of oral squamous cell carcinoma
Photodiagnosis and Photodynamic Therapy, 2006Co-Authors: Michele T. Cooper, Thomas S Mang, Maureen Sullivan, Thom R Loree, Nestor R RigualAbstract:PDT has been demonstrated in clinical studies to be an efficacious method for the treatment of dysplastic, microinvasive and early forms of cancer. The advantage of PDT for early carcinomas of the oral cavity is the ability to preserve normal tissues while effectively treating cancers up to 1cm in depth. The case presented here successfully demonstrates the ability to use PDT to treat maxillary gingival squamous cell carcinoma thereby sparing the use of surgery or radiation therapy at this point in the management of the disease.
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A dose ranging study of photodynamic therapy with Porfimer sodium (Photofrin®) for treatment of basal cell carcinoma
Lasers in Surgery and Medicine, 2006Co-Authors: Allan R. Oseroff, Leslie R. Blumenson, John C. Parsons, Noreen P. Frawley, B. Dale Wilson, Michele T. Cooper, Thomas S Mang, David A Bellnier, Nathalie C Zeitouni, Thomas J. DoughertyAbstract:Background and Objectives While basal cell carcinoma (BCC) is effectively treated by several methods, many patients with numerous or frequently occurring lesions seek alternatives that can treat multiple cancers, with improved cosmetic outcome. PDT for esophageal and lung carcinomas is approved at a Porfimer sodium (Photofrin®) dose of 2 mg/kg, but lower doses increase selectivity and decrease both cutaneous phototoxicity and cost. We evaluated low doses of Porfimer sodium PDT for treatment of multiple BCC. Materials and Methods Seventy-seven patients with 2,041 BCC were injected with 0.75, 0.875, or 1.0 mg/kg Porfimer sodium and treated 2 days later with 630-nm light. Clinical responses were determined at 6 months, then periodically to 5 years. Results Increasing Porfimer sodium dose increased complete responses (CR), with initial CR rates of 72.7% (66–78%, 95% CI), 79.9% (73–86%, 95% CI), and 92.2% (91–93%, 95% CI), albeit with some lower selectivity at the highest dose. At 1 mg/kg, 5-year recurrence rates were 28% (21–35%, 95% CI) and 15% (11–18%, 95% CI) for sporadic and nevoid basal cell carcinoma syndrome (NBCCS) lesions, respectively. Conclusions This is the largest dose-ranging study of Porfimer sodium, and the largest number of lesions treated in a single study. We found that with 1 mg/kg Porfimer sodium, PDT can be a selective and durable treatment for sporadic and NBCCS-associated BCC. Lasers Surg. Med. 38:417–426, 2006. © 2006 Wiley-Liss, Inc.
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evaluation of Porfimer sodium fluorescence for measuring tissue transformation
Cancer, 1993Co-Authors: David H Crean, Charles Liebow, Remedios B Penetrante, Thomas S MangAbstract:Background. Neoplastic tissue can be detected by its increased fluorescence compared with surrounding normal tissue after the injection of the tumor-localizing compound Porfimer sodium (Photofrin; Quadra Logic Technologies, Vancouver, BC, Canada). In vivo fluorescence photometry is a nonimaging photodetector technique that detects specific 690 nm fluorescence of the porphyrin by subtracting nonspecific 612 nm excitation from 630 nm excitation. The technique was applied in the developmental stages of the 9,10 dimethyl-l,2-benzanthracene (DMBA)-induced hamster buccal cheek pouch carcinoma model to (1) quantitate and characterize Porfimer sodium fluorescence and uptake as it relates to lesion progression and biochemical changes and (2) determine whether Porfimer sodium-induced fluorescence will vary with promotional and inhibitory stimuli. Methods. Groups of Syrian Golden hamsters had their cheek pouch buccal mucosa exposed to a 0.5% DMBA in acetone three times per week for 6 weeks (premalignant lesions), 12 weeks (squamous cell carcinomas), or other specified durations. The rate of malignant transformation was either promoted (by either carbon dioxide laser incision or continued DMBA application) or inhibited (by the administration of either somatostatin analogue RC-160 [D-Phe-Cys-Tyr-D-TrpLys-Val-Cys-Trp-NH,] or bombesin antagonist RC-3095 [ D - Tpi - Gln - Trp - Ala - Val - Gly -His - Leu$ (CH,NH) LeuNH,]). Groups of DMBA-exposed hamsters were subsequently injected with 1.0 mg/kg of Porfimer sodium during the various stages of tumor development. Twentyfour hours after injection, fluorescence levels were measured by in vivo fluorescence photometry. Samples of tumors, dysplastic mucosal tissue, and normal-appearing oral mucosa were biopsied and used for either tissue extraction assays, histopathologic examination, or tyrosine kinase activity assay as an index of rate of transformation. Results. Results demonstrated that Porfimer sodium is retained in DMBA-treated tissue. Fluorescence is completely accounted for by Porfimer sodium uptake. The duration of exposure to carcinogen is proportional to Porfimer sodium fluorescence. This relationship establishes that premalignant lesions can be distinguished from normal tissue by Porfimer sodium uptake and fluorescence. The changes in increased tyrosine kinase activity paralleled the increase in Porfimer sodium fluorescence. Alterations in the rate of tissue transformation produced equivalent alterations in Porfimer sodium-induced fluorescence. Conclusions. These results suggest that Porfimer sodium uptake and fluorescence can be used in a prognostic manner to diagnose and determine the course of transformation of individual lesions. Cancer 1993; 723068-77.
Kenneth K Wang - One of the best experts on this subject based on the ideXlab platform.
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verteporfin and sodium Porfimer mediated photodynamic therapy enhances pancreatic cancer cell death without activating stromal cells in the microenvironment
Journal of Biomedical Optics, 2019Co-Authors: Bhaskar Roy, Brian W. Pogue, Tayyaba Hasan, Marlys Anderson, Cadman L Leggett, Michael J Levy, Kenneth K WangAbstract:The goal of our study was to determine the susceptibility of different pancreatic cell lines to clinically applicable photodynamic therapy (PDT). The efficacy of PDT of two different commercially available photosensitizers, verteporfin and sodium Porfimer, was compared using a panel of four different pancreatic cancer cell lines, PANC-1, BxPC-3, CAPAN-2, and MIA PaCa-2, and an immortalized non-neoplastic pancreatic ductal epithelium cell line, HPNE. The minimum effective concentrations and dose-dependent curves of verteporfin and sodium Porfimer on PANC-1 were determined. Since pancreatic cancer is known to have significant stromal components, the effect of PDT on stromal cells was also assessed. To mimic tumor–stroma interaction, a co-culture of primary human fibroblasts or human pancreatic stellate cell (HPSCs) line with PANC-1 was used to test verteporfin-PDT-mediated cell death of PANC-1. Two cytokines (TNF-α and IL-1β) were used for stimulation of primary fibroblasts (derived from human esophageal biopsies) or HPSCs. The increased expression of smooth muscle actin (α-SMA) confirmed the activation of fibroblasts or HPSC upon treatment with TNF-α and IL-1β. Cell death assays showed that both sodium Porfimer- and verteporfin-mediated PDT-induced cell death in a dose-dependent manner. However, verteporfin-PDT treatment had a greater efficiency with 60 × lower concentration than sodium Porfimer-PDT in the PANC-1 incubated with stimulated fibroblasts or HPSC. Moreover, activation of stromal cells did not affect the treatment of the pancreatic cancer cell lines, suggesting that the effects of PDT are independent of the inflammatory microenvironment found in this two-dimensional culture model of cancers.
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squamous overgrowth is not a safety concern for photodynamic therapy for barrett s esophagus with high grade dysplasia
Gastroenterology, 2009Co-Authors: Mary P Bronner, Bergein F Overholt, Shari L Taylor, Rodger C Haggitt, Kenneth K Wang, Steven J Burdick, Charles J Lightdale, Michael B Kimmey, Hector R Nava, Michael V SivakAbstract:Background & Aims Photodynamic therapy with Porfimer sodium combined with acid suppression (PHOPDT) is used to treat patients with Barrett's esophagus (BE) with high-grade dysplasia (HGD). A 5-year phase 3 trial was conducted to determine the extent of squamous overgrowth of BE with HGD after PHOPDT. Methods Squamous overgrowth was compared in patients with BE with HGD randomly assigned (2:1) to receive PHOPDT (n = 138) or 20 mg omeprazole twice daily (n = 70). Patients underwent 4-quadrant jumbo esophageal biopsies every 2 cm throughout the pretreatment length of BE until 4 consecutive quarterly follow-up results were negative for HGD and then biannually up to 5 years or treatment failure. Endoscopies were reviewed by blinded gastroenterology pathologists. Results Histologic assessment of 33,658 biopsies showed no significant difference ( P > .05) in squamous overgrowth between groups when compared per patient (30% vs 33%) or per biopsy (0.5% vs 1.3%), or when the average number of biopsies with squamous overgrowth were compared per patient (0.48 vs 0.66). The highest grade of neoplasia per endoscopy was not found exclusively beneath squamous mucosa in any patient. Conclusions No difference was observed in squamous overgrowth between patients given PHOPDT plus omeprazole compared with only omeprazole. Squamous overgrowth did not obscure the most advanced neoplasia in any patient. Treatment of HGD with PHOPDT in patients with BE does not present a long-term risk of failure to detect subsquamous dysplasia or carcinoma.
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a 5 year randomized phase iii trial of efficacy and safety of photodynamic therapy using Porfimer sodium in high grade dysplasia in barrett s esophagus
Gastrointestinal Endoscopy, 2006Co-Authors: Bergein F Overholt, Kenneth K Wang, Steven J Burdick, Charles J Lightdale, Michael B Kimmey, Hector R Nava, Norman S Nishioka, Michael Sivak, Hugh Barr, Chad DavisAbstract:A 5-Year Randomized Phase III Trial of Efficacy and Safety of Photodynamic Therapy Using Porfimer Sodium in High-Grade Dysplasia in Barrett’s Esophagus Bergein Overholt, Kenneth Wang, Steven Burdick, Charles Lightdale, Michael Kimmey, Hector Nava, Michael Sivak, Norman Nishioka, Hugh Barr, Chad Davis, Norman Marcon, Marcos Pedrosa, Mary Bronner, Michelle Depot Purpose: Barrett’s esophagus (BE) with high-grade dysplasia (HGD) patients were enrolled in a two-year trial comparing photodynamic therapy (PDT) with Porfimer sodium (POR) plus 20 mg BID omeprazole (O) [PORPDT] with standard therapy of acid suppression with O [O alone] and followed for an additional 3 years. At 2 years, HGD ablation occurred in 77% of PORPDT patients versus 39% in O alone patients (p ! 0.0001). As HGD and possible cancer development in BE are inextricably linked, the trial was continued over 5 years to assess longer-term HGD ablation and cancer occurrence. Methods: Patients with BE and HGD were randomized (2:1) to PORPDT (n Z 138) or O alone (n Z 70). Patients on PDT received 2 mg/kg i.v. of POR followed by endoscopic laser light exposure of Barrett’s mucosa at a wavelength of 630 nm within 40-50 hours up to a maximum of 3 courses administered at least 90 days apart. Every 3 months, patients underwent 4-quadrant jumbo esophageal biopsies at 2-cm intervals. Pathologists based at one center assessed biopsies and were blinded to treatment assignment and patient identity. Results: At 5 years, PORPDT was significantly more effective than O alone in eliminating HGD (p ! 0.0001) and in preventing progression to cancer (p Z 0.027) with about twice the likelihood of cancer occurring in O alone (29%) compared to PORPDT (15%). HGD ablation at 5 years confirmed the significant difference found at 2 years (77% PORPDT, 39% O alone). Conclusions: This 5-year large randomized trial showed clearly that PORPDT is a statistically and clinically effective endoscopic therapy in eliminating HGD and in reducing the incidence of cancer in BE patients with HGD compared to O alone.
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photodynamic therapy with Porfimer sodium for ablation of high grade dysplasia in barrett s esophagus international partially blinded randomized phase iii trial
Gastrointestinal Endoscopy, 2005Co-Authors: Bergein F Overholt, Mary P Bronner, Shari L Taylor, Rodger C Haggitt, Kenneth K Wang, Charles J Lightdale, Marcia I Canto, Steven Burdick, Michael Grace, Michelle DepotAbstract:Background Barrett's esophagus (BE) may lead to high-grade dysplasia (HGD) and adenocarcinoma. The objective was to examine the impact of treating patients with BE and with HGD by using Porfimer sodium (POR) and photodynamic therapy (PDT) for ablating HGD and reducing the incidence of esophageal adenocarcinoma. Methods The design was a multicenter, partially blinded (pathology), randomized clinical trial conducted in patients with BE who have HGD. There were 30 contributing centers. A total of 485 patients were screened, with 208 in the intent-to-treat population and 202 in the safety population. Patients were randomized on a 2:1 basis to compare PDT with POR plus omeprazole (PORPDT) with omeprazole only (OM). The main outcome measurement was complete HGD ablation occurring at any time during the study period. Results There was a significant difference ( p p Conclusions PORPDT in conjunction with omeprazole is an effective therapy for ablating HGD in patients with BE and in reducing the incidence of esophageal adenocarcinoma.