The report of patients with lung cancer who could receive PDT combined with other modalities like surgery and chemotherapy is relatively rare. Combination of PDT and surgery is useful for multiple lung cancers (MPLC) or minimally invasive procedure to reduce resection line to peripheral site of superficial invasion in advanced lung cancer. Also, PDT combined with chemotherapy for advanced lung cancer with central airway stenosis seems to be usefull for local control and improvement of patient’s QOL.
MPLCs were noted in 22 (34.4%) of 64 patients treated with PDT using Laserphyrin (synchronous:10, and metachronous: 12). Among them, 10 patients (synch:2, meta:8) underwent surgery (lobectomy: 9, pneumonectomy: 1) for peripheral-type lung cancer as their first primary lesion followed by PDT for central type early stage lung cancer. CRs were achieved after PDT in all patients, and all patients were alive. We performed induction PDT to reduce resection line for 28 patents. Among them, histological type revealed squamous cell ca. in 24. Superficial invasion was recognized in trachea: 2, carina: 3, main bronchus or 2nd carina: 22. Reduction surgery could be successfully performed in 23 of 28 patients (82%). PDT combined with chemotherapy was performed for 12 consecutive patients with 13 advanced NSCLC whose stages were IIIA–IV. The median stenosis rates before treatment, 1 week, and 1 month after treatment were 60%, 15%, and 15%, respectively. All patients improved symptoms and QOL after treatment. The mean survival time was 5.9 months, and the overall one-year survival rate was 30.0%.PDT combined with other modalities may be a promising strategy in lung cancer treatment.
The effectiveness of a new excimer laser endoscopic imaging fluorescence analyzer system using the photosensitizer, mono-L-aspartyl chlorin e6 (NPe6) for the detection of tumors was evaluated. Autofluorescence (550 plus or minus 10 nm, green fluorescence) from normal sites, red fluorescence (664 nm) of NPe6 in areas of cancer and the red fluorescence/green fluorescence ratio (R/G ratio) as the color image can be detected respectively. The greatest NPe6 fluorescence from the lesion was obtained at 3 hours after injection and the fluorescence disappeared at 24 hours. The greatest difference in the fluorescence of NPe6 and the R/G ratio in areas of tumor and in normal areas were observed at 5 hours after administration. At this period, NPe6 fluorescence from normal sites was negligible. These data suggest that fluorescence photodiagnosis may be effective in the detection of cancers.
The authors developed a new high-power red laser diode system (Matsushita Industrial Equipment Co., Ltd., Osaka) for photodynamic therapy (PDT) with mono-L-aspartyl chlorin e6 (NPe6, Meiji Seika Kaisha LTD.). The laser wavelength was adjusted to 664 nm and the power output could be varied in the range of 50-500 mW at the fiber tip in a continuous wave (cw) mode. The delivered energy could be adjusted from 50 - 1000 J. The system has a size of 49 by 20 by 40 cm, weighs 20 kg, and is readily portable. It runs on 100 V current. The laser power is easily controlled and the wavelength is stable (less than plus or minus 0.2 nm). The output beam is delivered via a quartz fiber. Furthermore, the full width at half-maximum power is less than 2 nm, which enables uniform, high-density photoirradiation. The power density distribution of the laser, analyzed by a CCD camera, was uniform throughout the photoirradiated field. In an animal study, tumor-bearing Balb/c mice were treated with the diode laser 5 hours after intravenous administration of NPe6 at a dose of 1.25 to 12.5 mg/kg i.v.. Total photoirradiation ranged from 3.13 to 250 J/cm2 which the energy density was adjusted to 100 mW/cm2. Percentages of cures were determined histopathologically from numbers of mice apparently disease-free 1 week after treatment. The results show that a laser energy of more than 12.5 J/cm2 was necessary to obtain 90% tumor cure rate at a maximum dose of NPe6 (12.5 mg/kg) and NPe6 dose of more than 2.5 mg/kg was necessary to obtain 90% cure rate at high laser energy of 200 J/cm2.
We investigated the in vivo fluorescence detection of premalignant and malignant lesions in carcinogen-induced tumors of the hamster buccal cheek pouch and micrometastases in rat lymph nodes using hexylpyropheophorbide-a (HPPH) at 0.5 mg/kg and He-Ne laser-induced fluorescence photometry. Time course studies of HPPH in hamster tumor model showed maximal relative fluorescence readings at 48 hours after i.p. injection in each stage (dysplasia: 0.35, papilloma: 0.58, squamous cell carcinoma: 1.04). Squamous cell carcinoma showed significantly greater fluorescence than papillomas and dysplasias at all time points (p < 0.01). Metastatic lymph nodes were significantly greater than normal lymph nodes at all time points (p < 0.01). Maximal fluorescence levels of normal lymph nodes were observed at 6 hours after i.v. injection. Metastatic lymph nodes still showed high fluorescence levels at 72 hours. Micrometastases showed fluorescence levels between the levels of metastatic and normal lymph nodes (normal: 0.40 < micrometastasis: 0.62 < metastasis: 0.75 at 48 hours after i.v. injection). The results demonstrated good correlation between fluorescence levels and histopathological developments at all time points. Therefore, HPPH may be a promising fluorophore for the detection of developing malignancies and occult disease.
Recently, a new photosensitizer, 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-1 (HPPH) was developed for PDT which possesses more rapid clearance from skin and greater cytotoxicity per drug dose than Photofrin. The spectral characteristics of HPPH shows an absorption band at 665 nm (50,000 M-1cm(superscript -1 and peak emission at 680 nm. The aid of this study was to examine HPPH as a fluorescent diagnostic compound for the detection of transformed tissues using the in vivo fluorescence photodetector. The model of tissue transformation was the carcinogen (DMBA [9, 10-dimethyl-1, 2- benzanthracene])-induced premalignant and malignant lesions of the hamster buccal cheek pouch. The results demonstrated significant correlations between fluorescence levels and histological developments at all time points after injection. Time course studies of HPPH showed highest fluorescence readings at 48 hours after injection of 0.5 mg/kg HPPH (mild-moderate dysplasia, 0.35 +/- 0.17 volts; papillary disease with severe dysplasia, 0.58 +/- 0.33 volts; and squamous cell carcinoma, 1.04 $OM 0.32 volts). Therefore, it appears that HPPH may be a promising fluorophore for the detection of transformed tissues.