Photodynamic therapy of locoregional breast cancer recurrences using a chlorin-type photosensitizer.

Chest wall recurrences are a frequent problem in patients treated by mastectomy for breast cancer. Surgery and ionizing radiation are established treatment modalities in these cases. Photodynamic therapy (PDT) provides an alternative treatment modality using a photosensitizer and laser light to induce selective tumor necrosis. PDT was performed as compassionate use in 7 patients aged 57.6 years (+/-12.6 SD). A total of 89 metastatic skin nodes were treated in 11 PDT sessions. As photosensitizer meta-tetra(hydroxyphenyl)chlorin (m-THPC) was applied intravenously. Patients (n = 3) photosensitized with a drug dose of 0.10 mg/kg bodyweight were irradiated 48 hr after drug application at a lightdose of 5 J/cm(2). Patients (n = 4) were illuminated by an optical dose of 10 J/cm(2) 96 hr after photosensitization with 0.15 mg/kg. Laser light at a wavelength of 652 nm was generated by a diode laser and applied by a front lens light diffuser using a fluence rate of 20--25 mW/cm(2). PDT using m-THPC resulted in complete response in all patients. Response to treatment did not differ when using the 2 different drugdose protocols. Healing time depended mainly on the size of the illumination field but not on the lightdose. Pain score usually raised 1 day after PDT and lasted at higher levels for about 10 days. Healing time usually ranged between 8--10 weeks. Photodynamic technique offers a minimal-invasive, outpatient treatment modality for recurrent breast cancer on the chest wall with few side effects, high patient's satisfaction and with possible repetitive application.

Hypercalcemic-type of small cell carcinoma of the ovary: characterization of a new tumor line.

BACKGROUND: The aim of this study was to develop and characterize a mouse xenograft model for the hypercalcemic-type of small cell carcinoma of the ovary (HTSCCO). PATIENTS AND METHODS: Tumor fragments were removed from a patient and cultured in six subsequent generations of nude mice. Histology, comparative genomic hybridization (CGH), electron microscopy and serum calcium levels were investigated. RESULTS: Morphology remained the same from the primary tumor of the patient through the 6th passage in the mouse. Serum calcium levels were significantly higher in the tumor-bearing mice compared to controls. CGH of the HTSCCO did not show evidence of a close relationship to either a germ cell tumor or an epithelial ovarian cancer. CONCLUSION: Some evidence was provided that the HTSCCO is an inhomogeneous tumor that is neither related to a germ cell tumor nor to an epithelial ovarian cancer, but is a distinct tumor entity.

Prognostic significance of CA 125 and TPS levels after 3 chemotherapy courses in ovarian cancer patients.

OBJECTIVE: To evaluate the prognostic significance of and predictive value for survival of CA 125 and TPS levels after three chemotherapy courses in ovarian cancer patients. METHODS: We analyzed in a prospective multicenter study the 1- and 2-year overall survival (OS) in ovarian carcinoma patients. The prognostic significance of CA 125 and TPS levels above the discrimination value (25 kU/L and 100 U/L, respectively) was examined by univariate and multivariate analyses. RESULTS: Of the 213 cases included, 64 patients were staged as FIGO I + II and 149 patients were staged as FIGO III + IV. Tumor marker levels in stage I + II were not correlated with survival. However, stage III and IV patients with elevated levels of CA 125 or TPS after three chemotherapy courses had a worse 2-year OS (69% vs 26%, P < 0.0001 and 57% vs 20%, P < 0.0001, respectively) than patients with normal levels of the markers. In univariate analysis the result of operation (staging laparatomy and partial debulking) and advanced FIGO stage (IV) were also adverse prognostic factors. Independent factors predictive of low 2-year OS by multivariate analysis were staging laparotomy, TPS elevated, and CA 125 elevated. The only factors predictive of low 1-year OS were TPS elevated and staging laparotomy. CONCLUSIONS: Ovarian cancer patients with elevated CA 125 levels after three chemotherapy courses have a poor prognosis. However, the prognostic accuracy can be significantly increased by the parallel determination of serum TPS.

Photodynamic therapy for the hypercalcemic type of the small cell carcinoma of the ovary in a mouse xenograft model.

OBJECTIVE: The hypercalcemic type of the small cell carcinoma of the ovary (HTSCCO) is a rapidly fatal ovarian tumor in young women. Photodynamic therapy (PDT) induces selective necrosis to malignant tissues. The aim of this study was to determine the sensitivity of the HTSCCO to PDT in a mouse xenograft model. METHODS: Tumors were obtained from a patient with a HTSCCO and were transplanted into nude mice. Following photosensitization with m-THPC, either superficial or interstitial laser light was administered to the tumors. Necroses were measured by morphometry. Serum calcium levels were determined prior to and after PDT. RESULTS: Superficial irradiation of m-THPC sensitized tumors showed over three times more necrosis than control tumors (P = 0.037). Interstitially irradiated tumors showed over seven times more necrosis than control tumors (P = 0.0012). All animals showed a highly significant hypercalcemia prior to PDT (P < 0.0001). PDT induced a significant decrease in serum calcium levels (P = 0.0297). CONCLUSION: This study suggests that PDT may be of therapeutic value for the HTSCCO.

Enhanced photodynamic effects using fractionated laser light.

Photodynamic eradication of tumour cells depends on the presence of a photosensitizer and light delivery to the cells. The present study investigated the influence of fractionated light (on-off mode) on cell killing as documented by a colony-forming assay. Photosensitizers were m-THPC (ethanol soluble, Foscan) and m-THPC-MD (water soluble, both from Scotia Pharmaceuticals, Guildford, UK). Fractionated laser light at a wavelength of 652 nm with a light duration of 0.05 s was more effective than continuous illumination at the same power density for both photosensitizers. We propose that fractionated laser light is more toxic due to short phases of recovery during the dark intervals, probably resulting in more singlet oxygen under these conditions. By use of Foscan, for example, and fractionated laser light, a similar effect is expected for the treatment of solid tumours. In this case we expect improvements in photodynamic therapy (PDT) for patients by lowering the concentrations of photosensitizer and/or by reducing the applied light dose.

[The combined use of photodynamic therapy with ionizing radiation on breast carcinoma cells in vitro]. / Kombinierte Anwendung der photodynamischen Therapie mit ionisierenden Strahlen bei Mammakarzinomzellen in vitro.

PURPOSE: The photodynamic therapy is a technique by which the tumor cells are selectively sensitized to destruction by light of an appropriate wavelength. The aim of this work is to analyze the biological effectiveness of photochemical reactions induced by laser light in tumor cells exposed to photosensitizers. MATERIAL AND METHODS: The toxicity of the 2 photosensitizers zinc phthalocyanine (ZnPC) and meso-tetrahydroxyphenylchlorine (m-THPC) as well as the biological effect of the combination of sensitizers with laser light were tested in vitro by means of a colony forming assay. In addition, the influence on the photodynamic reaction of a previous exposure of the tumor cells to ionizing radiation has been tested. RESULTS: For both sensitizers doses of 5 micrograms per milliliter of culture medium showed low toxicity, i.e. the survival of the treated cells exceeded 90%. For laser treatments the dose permitting 90% survival was determined to be around 10 J/cm2. With these doses, the combined application of photosensitizers and laser light proved to be very effective and resulted in a nearly complete reduction of survival. As expected, irradiation of the cells with doses of 1 and 2 Gy of X-rays reduced the survival to 66 and 47%, respectively, compared to untreated controls. Cells surviving such treatment showed no changes either in the response to treatments with photosensitizers or to combined applications of photosensitizers and laser light. CONCLUSION: The effects of photodynamic treatment by ionizing radiation seem to be additive and independent of each other. So, our preliminary results are quite encouraging and point out the need of further detailed studies in view of the intended clinical application of this new kind of a local treatment.