The Effects of Photodynamic Therapy with Photogem and Laser with Power Density of 600 mW/cm2 on Lewis Lung Carcinoma Cells Tumor Graft in Mouse

PURPOSE: Photodynamic therapy was used to lung cancer. We have made a light microscpic study on the effects of photodynamic therapy to tumor graft in skin of mice, when the power density was 600 mW/cm2 with reducing time. MATERIALS AND METHODS: These studies had been performed on sixteen C57BL/6 mice that Lewis lung carcinoma cells had been implanted. All mice were divided into four groups. One of four groups received Photogem 3 mg/kg intravenously 24 hours prior to exposure of tumor to 180 J/cm2 laser light vertically at a wavelength 635etam with a higher power density of 600 mW/cm2 than that of 400 mW/cm2 clinically. One of these group received only Photogem. The others not received Photogem and one of these irradiated with laser. The light source was the wavelength of 635 etam Diode Laser (Laxcell 2004, Bio- Optics. co. Korea) After photodynamic therapy was finished, staining and analysing of tumors were used to determine the natures and extents of injury. RESULTS: Grossly response was not observed. Histologically, there were loss of endothelium from small vessel at tumor and muscle with thrombus formation. There were focal necrosis with infiltration of inflammatory cells at tumor and adjacent tissues that irradiated with laser, regardless of administration of Photogem. CONCLUSION: Photodynamic therapy using Photogem and LASER with power density of 600 mW/cm2 destroy not only tumors incompletely but also adjacent normal tissue.

Multimodality Treatement in Patients with Clinical Stage IIIA NSCLC / 결핵및호흡기질환

BACKGROUND: To find out effectiveness of multimodality treatments based on induction chemotherapy(CTx) in patients with clinical stage IIIA NSCLC METHODS: From 1997 to 2002, 74 patients with clinical stage IIIA NSCLC underwent induction CTx at the hospital of Chungnam National University. Induction CTx included above two cycles of cisplatin-based regimens(ectoposide, gemcitabine, vinorelbine, or taxol) followed by tumor evaluation. In 30 complete resection group, additional 4500-5000cGy radiotherapy(RTx) was delivered in 15 patients with pathologic nodal metastasis. 29 out of 44 patients who were unresectable disease, refusal of operation, and incomplete resection were followed by 60-70Gy RTx in local treatment. Additional 1-3 cycle CTx were done in case of induction CTx responders in both local treatment groups. RESULTS: Induction CTx response rate were 44.6%(complete remission 1.4% & partial response 43.2%) and there was no difference of response rate by regimens(p=0.506). After induction chemotherapy, only 33 out of resectable 55 ones(including initial resectable 37 patients) were performed by surgical treatment because of 13 refusal of surgery by themselves and 9 poor predicted reserve lung function. There were 30(40.5%) patients with complete resection, 2(2.6%) persons with incomplete resection, and 1(1.3%) person with open & closure. Response rate in 27 ones with chest RTx out of non-operation group was 4.8% CR and 11.9% PR. In complete resection group, relapse free interval was 13.6 months and 2 year recur rate was 52%. In non-complete resection(incomplete resection or non-operation) group, disease progression free interval was 11.2 months and 2 year disease progression rate was 66.7%. Median survival time of induction CTx 74 patients with IIIA NSCLC was 25.1months. When compared complete resection group with non-complete resection group, the median survival time was 31.7 and 23.4months(p=0.024) and the 2-year overall survival rate was 80% and 41% . In the complete resection group, adjuvant postoperative RTx subgroup significantly improved the 2-year local control rate(0% vs. 40%, p= 0.007) but did not significantly improve overall survival(32.2months vs. 34.9months, p=0.48). CONCLUSION: Induction CTx is a possible method in the multimodality treatments, especially followed by complete resection, but overall survival by any local treatment(surgical resection or RTx) was low. Additional studies should be needed to analysis data for appropriate patient selection, new chemotherapy regimens and the time when should RTx be initiated.

Factors Predicting the Development of Radiation Pneumonitis in the Patients Receiving Radiation Therapy for Lung Cancer / 결핵

BACKGROUND: Radiation pneumonitis(RP) is the major serious complication of thoracic irradiation treatment. In this study, we attempted to retrospectively evaluate the long-term prognosis of patients who experienced acute RP and to identify factor that might allow prediction of RP. METHODS: Of the 114 lung cancer patients who underwent thoracic radiotherapy between December 2000 and December 2002, We performed analysis using a database of 90 patients who were capable of being evaluated. RESULTS: Of the 44 patients(48.9%) who experienced clinical RP in this study, the RP was mild in 33(36.6%) and severe in 11(12.3%). All of severe RP were treated with corticosteroids. The median starting corticosteroids dose was 34 mg(30~40) and median treatment duration was 68 days(8~97). The median survival time of the 11 patients who experienced severe RP was significantly poorer than the mild RP group. (p=0.046) The higher total radiation dose(>or=60 Gy) was significantly associated with developing in RP.(p=0.001) The incidence of RP did not correlate with any of the ECOG performance, pulmonary function test, age, cell type, history of smoking, radiotherapy combined with chemotherapy, once-daily radiotherapy dose fraction. Also, serum albumin level, uric acid level at onset of RP did not influence the risk of severe RP in our study. CONCLUSION: Only the higher total radiation dose(>or=60 Gy) was a significant risk factor predictive of RP. Also severe RP was an adverse prognostic factor.

The Histological Changes of Photodynamic Therapy Using 635 nm Diode Laser on Normal Tissues of C57BL/6 Mouse Model

PURPOSE: Photodynamic therapy, with photosensitizer and non-thermal laser, produces selective destruction of cancer without affecting the adjacent normal tissues. The aim of our study was to evaluate the pathological changes to the normal tissues when photodynamic therapy, with non-thermal laser irradiation, after the administration of a photosensitizer. MATERIALS AND METHODS: Studies were performed on four C57BL/6 mouse models using a photosensitizer (Photogem(R), Moscow Institute of High Chemical Technologies). The mice received Photogem, 3 mg/kg i.v., 24 hours prior to the exposure of normal tissues to 180 J/cm2 laser light, at a wavelength and power density of 635 nm and 600 mW/cm2, respectively, with the light source being a 635 nm Diode Laser (Laxcell 2004, Bio-Optics. co.) Histological staining and analysis were used to determine the nature and extent of injury at the first, third, fifth, and seventh days after the photodynamic therapy. RESULTS: Histologically, there were losses of endothelium from small vessels in the skin and muscle, with focal necrosis and diffuse inflammatory changes in the adjacent tissues. Between the fifth and seventh days following the photodynamic therapy, generation of granulation tissue, composed of fibroblasts and endothelial cells was observed surrounding the necrotic area. CONCLUSION: Photodynamic therapy using Photogem and a 635 nm Diode Laser, with a power density of 600 mW/cm2, develops non-selective necrosis and has a thermal effect on normal tissue

Detection of Brain Metastatses Using Limited Brain MR Imaging ; Usefulness of Limited Contrast-Enhanced MR Imaging in Brain Metastasis / 결핵

BACKGROUND: The brain is a common site of a metastasis in lung cancer patients. If left untreated, the patients succumb to progressive neurological deterioration with a lower survival rate than with other metastases sites. Contrast-enhanced MR imaging in the absence of symptoms or clinical signs is not recommended for identifying a cerebral metastasis in lung cancer patients because of management effectiveness. This pilot study was performed to estimate whether or not limited brain MR imaging, which has a lower cost, could be used to replace conventional brain MR imaging. METHOD: Between April 1999 and March 2001, 43 patients with a primary lung cancer and the others (breast cancer, stomach cancer, colon cancer, malignant melanoma etc), who had neurological symptoms and signs, were examined using conventional brain MR imaging to examine brain metastases. The control group involved four patients who had no evidence of brain metastases the sensitivity, specificity and correlation of limited brain MR imaging were compared with conventional brain MR imaging. RESULTS: All the 43 patients who were examined with conventional brain MR imaging showed evidence of brain metastases, whereas limited brain MR imaging indicated that 42 patients had brain metastases(sensitivity=97.67%). One patient in whom limited brain MR imaging showed no brain metastasis had a metastasis in the cerebellum, as shown by the contrast-enhanced T1 weighted axial view using conventional brain MR imaging. The conventional brain MR imaging and the limited brain MI imaging of the 4 control patients both indicated no brain metastases (specificity=100 %). The Pearson Correlation of the two groups was 0.884(Confidence Interval : 99%) observed. CONCLUSION: Limited brain MR imaging can detect a brain metastasis with the same accuracy. In addition, it is cost-effective (229,000 won, 180$) compared to conventional brain MR imaging(529,000 won, 480$) when patients had neurological symptoms and signs or staging.

Vinorelbine Monotherapy on Advanced Non-small Cell Lung Cancer / 결핵

BACKGROUND: Unresectable non-small cell lung cancer has a poor response to chemotherapy and has an unfortunate prognosis. More effective and less toxic cytotoxic agents are needed to improve the outcome of these pa tients. The efficacy and safety of vinorelbine monotherapy in these advanced lung cancer patients was evaluated. METHODS: Sixteen patients with non-small cell lung cancer in stage III or IV, who received vinorelbine alone as an intial anticancer chemotherapy from June 1996 to December 2000 were enrolled in this study. Vinorelbine was given intravenously at a dose 30mg/m2 every weel. RESULTS: Among the sixteen patients, six had a partial response (38%) and the median survival was 16 weeks. The median response duration was 27 weeks (95% CI 6-47), and the time to progression was 16 weeks (95% CI 6-26). Among a ttal of 112 cycles, neutropenia (WHO grade 3 or 4) and anemia (grade 3) occurred in 9% and 3%, respectively. Only 1 patients required hospitalization for neutropenic fever. Non-hematologic toxicity was monor and was easily controlled. CONCLUSION: Vinorelbine monotherapy was well tolerated, and moderatly effective in patients with advanced non-small cell lung cancer.

Prognostic Factors for Survival in Patients with Stage IV Non-small Cell Lung Cancer / 결핵

BACKGROUND: Although patients with stage IV non-small cell lung cancer areknown to have a poor prognosis, the prognostic factors for survival have not been well evaluated. Such factors may be different from those for overall survival. This study was performed to analyze the prognostic factors for survival and the variation of survival according to metastatic organ, in patients with stage IV non-small cell lung cancer. MATERIALS AND METHODS: From January 1997 to December 2000, 151 patients with confirmed stage IV non-small cell lung cancer were enrolled into this study retrospectively. The clinical and laboratory data were analyzed using univariate Kaplan-Meier and Multivariate Cox regression models. RESULTS: On univariate analysis, age, performance status, serum albumin level, weight loss, forced expiratory volume in one second (FEV1), systemic chemotherapy, the number of metastatic organs and serum lactate dehydrogenase (LDH) level were significant factors (p<0.05). In multivariate analysis, important factors for survival were ECOG performance (relative risk of death [RR]: 2.709), systemic chemotherapy (RR: 1.944), serum LDH level (RR: 1.819) and FEV1 (RR: 1.774) (p<0.05). Metastasis to the brain and liver was also a significant factor on univariate analysis). The presence of single lung metastasis was associated with better survival than that of other metastatic organs (p=0.000). CONCLUSION: We confirmed that performance status and systemic chemotherapy were independent prognostic factors, as has been recognized. The survival of stage IV non-small cell lung cancer patients was different according to the metastatic organs. Among the metastatic sites, only patients with metastasis to the lung showed better survival than that of other sites, while metastasis of the brain or liver was associated with worse survival than that of other sites.