Effects of electrophotodynamic therapy in vitro on human melanoma cells--melanotic (MeWo) and amelanotic (C32).

Photodynamic therapy has been considered ineffective for melanomas because of the competition between the absorbance of melanin from the melanoma and the absorbance of photosensitizers at the photosensitizer excitation light wavelength. Melanomas show considerable heterogeneity and resistance to phototherapy. The effectiveness of photodynamic therapy could be intensified by electroporation for enhanced transport of a photosensitizer by transient pores in the membrane. In this study, photodynamic therapy combined with electroporation was tested in vitro on the human melanoma cell lines melanotic melanoma (MeWo) and amelanotic melanoma (C32). Control experiments were conducted on human keratinocytes (HaCaT). Photofrin was used as a photosensitizer. Photosensitizer distribution, cloning efficacy test, comet assay, and assessment of apoptotic proteins were performed. Melanin levels were determined before and after photodynamic therapy. The experiments indicated that electroporation effectively supports the photodynamic method. It was found that photodynamic therapy with electroporation efficiently induces apoptosis in melanotic and amelanotic melanoma cells.

Nonoperable patients with superficial esophageal cancer treated by photodynamic therapy after chemoradiotherapy have more severe complications than patients treated in primary intent.

INTRODUCTION: Photodynamic therapy (PDT) is a therapeutic option in patients with a superficial esophageal cancer. Recently, PDT was shown to be effective as a salvage therapy for a local recurrence after chemoradiotherapy (CRT). AIM: To compare retrospectively the results and the complications rate of PDT between consecutive patients treated in primary intent for a superficial esophageal cancer versus patients treated by PDT for a local recurrence after CRT. METHODS: Between 1999 and 2007 in a single center, 40 consecutive patients were treated by PDT for a superficial esophageal cancer, 25 (group 1) in primary intent and 15 (group 2) for a local recurrence after CRT. Two days after intravenous (IV) Photofrin (2 mg/kg), the phototherapy was performed with a dye laser. The treatment response and severe complications, defined as perforation and stricture requiring endoscopic dilation, were compared between the two groups. RESULTS: The patient and tumor characteristics were not different between the two groups. In group 1, 19 out of 25 patients (76%) were successfully treated versus 8 out of 15 patients (53%) in group 2 (P= 0.17). Severe complications occurred more frequently in patients with a prior CRT (8%vs 46.7%, P= 0.008) and included two perforations and five strictures requiring endoscopic dilation, while only two strictures occurred in group 1. A prior CRT was an independent risk factor of severe complications (odds ratio [OR] 8.05; 95% confidence interval [CI]1.22-43.0). CONCLUSIONS: Severe complications were significantly more frequent in patients treated after a prior CRT. PDT as a salvage therapy in patients with a local recurrence after CRT for esophageal cancer tended to be less efficient than in first-line treatment.

Patient predictors of esophageal stricture development after photodynamic therapy.

BACKGROUND & AIMS: The most common significant adverse event after photodynamic therapy (PDT) with porfimer sodium is esophageal stricture formation. This study assessed whether pretreatment variables, including prior endoscopic therapy for Barrett's esophagus, are associated with post-PDT stricturing. METHODS: Data from all patients who had undergone PDT with porfimer sodium for Barrett's esophagus with high-grade dysplasia, intramucosal carcinoma, or T1 cancer at our institution since 1997 were reviewed. RESULTS: One hundred sixteen patients underwent 160 courses of PDT. The incidence of stricture formation after index PDT was 16% (19/116). For all PDT courses, the overall incidence of stricture was 23% (37/160). Stricture rate was significantly higher after a second PDT course compared with index PDT (43% vs 16%, P = .0007). There was no association between post-PDT stricture development and age, gender, body mass index, or prior endoscopic mucosal resection. Patients who developed a stricture had a longer length of Barrett's esophagus before treatment than those who did not develop a stricture (7.7 vs 5.7 cm for index PDT only, P = .025; 7.4 vs 5.7 cm for all PDT courses, P = .007). Length of Barrett's esophagus, multiple PDT courses, and presence of intramucosal carcinoma on pretreatment pathology were independent predictors of post-PDT stricture in a stepwise logistic regression analysis controlling for treatment variables, including treatment length. CONCLUSIONS: An increased risk of stricture development was seen after multiple courses of PDT. An association between post-PDT stricture and length of Barrett's esophagus but not treatment length was also found. Endoscopic mucosal resection did not appear to influence the likelihood of stricture development after porfimer sodium-based PDT.

Photodynamic therapy for cervical intraepithelial neoplasia.

OBJECTIVES: Photodynamic therapy (PDT) is a minimally invasive treatment for cervical intraepithelial neoplasia (CIN). We report the effectiveness of PDT in 105 cases of CIN. METHODS: All patients received photofrin (PHE) 2 mg/kg intravenously and, 48-60 h later, phototherapy was performed using the Excimer dye laser or a YAG-OPO laser with an irradiation dose of 100 J/cm(2) using 630 nm wavelength. RESULTS: Mild photosensitivity occurred in 48% (50/105) of patients. The complete response (CR) rate was 90% (94/105) at 3 months following treatment. In the remaining 11 patients, 5 patients had CIN1, 2 patients had CIN2, and 4 patients had mild cytologic findings. However, in 9 of these 11 patients, CR was achieved 6 months after PDT. In 69 patients, human papilloma virus (HPV) typing was performed before and after PDT therapy. Pre-treatment, 64 of 69 patients (93%), were HPV-positive including 30 cases of high-risk HPV (43%). Testing performed 3, 6 and 12 months following PDT revealed no HPV-DNA in 75% (52/69), 74% (48/65) and 72% (41/57) of patients. At present, the median follow-up period is 636 days (90-2,232 days). In 3 patients, recurrence requiring surgical treatment was identified at 646, 717 and 895 days after PDT. CONCLUSIONS: PDT is an effective and minimally invasive treatment for CIN, which also appears to eradicate HPV infection.

Preliminary report of photodynamic therapy for intraperitoneal sarcomatosis.

INTRODUCTION: Sarcomatosis is the disseminated intraperitoneal spread of sarcoma. It is a condition for which there is no effective treatment. Photodynamic therapy (PDT) is a cancer treatment modality that uses a photosensitizing agent and laser light to kill cells. We report our preliminary Phase II clinical trial experience using PDT for the treatment of intraperitoneal sarcomatosis. METHODS: From May 1997 to December 1998 eleven patients received twelve PDT treatments for intraperitoneal sarcomatosis. Photofrin (PF) 2.5 mg/kg was administered intravenously 48 hours before surgical debulking to a maximum residual tumor size of less than 5 mm. Light therapy was administered at a fluence of 2.5 J/cm2 of 532 nm green light to the mesentery and serosa of the small bowel and colon; 5 J/cm2 of 630 nm red light to the stomach and duodenum; 7.5 J/cm2 of red light to the surface of the liver, spleen, and diaphragms; and 10 J/cm2 of red light to the retroperitoneal gutters and pelvis. Light fluence was measured with an on-line light dosimetry system. Response to treatment was evaluated by abdominal CT scan at 3 and 6 months, diagnostic laparoscopy at 3 to 6 months, and clinical examination every 3 months. RESULTS: Adequate tumor debulking required an omentectomy in eight patients (73%), small bowel resection in seven patients (64%), colon resection in four patients (36%), splenectomy in one patient (9%), and a left spermatic cord resection in one patient. Five patients (45%) have no evidence of disease at follow-up (range, 1.7-17.3 months), including patients at 13.8 and 17.3 months examined by CT. Two patients (18%) died from disease progression. Four patients (36%) are alive with disease progression. Toxicities related to PDT included substantial postoperative fluid shifts with volume overload, transient thrombocytopenia, and elevated liver function tests. One patient suffered a postoperative pulmonary embolism complicated by adult respiratory distress syndrome (ARDS). CONCLUSIONS: Debulking surgery with intraperitoneal PDT for sarcomatosis is feasible. Preliminary response data suggest prolonged relapse-free survival in some patients. Additional follow-up with more patients will be necessary for full evaluation of the added benefit of PDT and aggressive surgical debulking in these patients.