Effectiveness of Fentanyl Transdermal Patch (Fentanyl-TTS, Durogegic(R)) for Radiotherapy Induced Pain and Cancer Pain: Multi-center Trial / 대한방사선종양학회지

PURPOSE: To evaluate the effectiveness and safety of fentanyl-TTS in the management of radiotherapy induced acute pain and cancer pain treated with radiotherapy. MATERIALS AND METHODS: Our study was open labelled prospective phase IV multi-center study. the study population included patients with more 4 numeric rating scale(NRS) score pain although managed with other analgesics or more than 6 NRS score pain without analgesics. Patients divided into two groups; patients with radiotherapy induced pain (Group A) and patients with cancer pain treated with radiotherapy (Group B). All patients received 25 ug/hr of fentanyl transdermal patch. Primary end point was pain relief; second end points were change in patient quality of life, a degree of satisfaction for patients and clinician, side effects. RESULTS: Between March 2005 and June 2005, 312 patients from 26 participating institutes were registered, but 249 patients completed this study. Total number of patients in each group was 185 in Group A, 64 in Group B. Mean age was 60 years and male to female ratio was 76:24. Severe pain NRS score at 2 weeks after the application of fentanyl was decreased from 7.03 to 4.01, p=0.003. There was a significant improvement in insomnia, social functioning, and quality of life. A degree of satisfaction for patients and clinician was very high. The most common reasons of patients' satisfactions was good pain control. Ninety six patients reported side effect. Nausea was the most common side effect. There was no serious side effect. CONCLUSION: Fentanyl-TTS was effective in both relieving pain with good tolerability and improving the quality of life for patients with radiotherapy induced acute pain and cancer pain treated with radiotherapy. The satisfaction of the patients and doctors was good. There was no major side effect.

The 1998, 1999 Patterns of Care Study for Breast Irradiation After Breast-Conserving Surgery in Korea / 대한방사선종양학회지

PURPOSE: To determine the patterns of evaluation and treatment in the patient with early breast cancer treated with conservative surgery and radiotherapy and to improve the radiotherapy techiniques, nationwide survey was performed. MATERIALS AND METHODS: A web-based database system for Korean Patterns of Care Study (PCS) for 6 common cancers was developed. Two hundreds sixty-one randomly selected records of eligible patients treated between 1998~999 from 15 hospitals were reviewed. RESULTS: The patients ages ranged from 24 to 85 years(median 45 years). Infiltrating ductal carcinoma was most common histologic type (88.9%) followed by medullary carcinoma (4.2%) and infiltrating lobular carcinoma (1.5%). Pathologic T stage by AJCC was T1 in 59.7% of the casses, T2 in 29.5% of the cases, Tis in 8.8% of the cases. Axillary lymph node dissection was performed in 91.2% of the cases and 69.7% were node negative. AJCC stage was 0 in 8.8% of the cases, stage I in 44.9% of the cases, stage IIa in 33.3% of the cases, and stage IIb in 8.4% of the cases. Estrogen and progesteron receptors were evaluated in 71.6%, and 70.9% of the patients, respectively. Surgical methods of breast-conserving surgery was excision/lumpectomy in 37.2%, wide excision in 11.5%, quadrantectomy in 23% and partial mastectomy in 27.5% of the cases. A pathologically confirmed negative margin was obtained in 90.8% of the cases. Pathological margin was involved with tumor in 10 patients and margin was close (less than 2 mm) in 10 patients. All the patients except one recieved more than 90% of the planned radiotherapy dose. Radiotherapy volume was breast only in 88% of the cases, breast+supraclavicular fossa (SCL) in 5% of the cases, and breast+SCL+posterior axillary boost in 4.2% of the cases. Only one patient received isolated internal mammary lymph node irradiation. Used radiation beam was Co-60 in 8 cases, 4 MV X-ray in 115 cases, 6 MV X-ray in 125 cases, and 10 MV X-ray in 11 cases. The radiation dose to the whole breast was 45~9.4 Gy (median 50.4) and boost dose was 8~20 Gy (median 10 Gy). The total radiation dose delivered was 50.4~70.4 Gy (median 60.4 Gy). CONCLUSION: There was no major deviation from current standard in the patterns of evaluation and treatment for the patients with early breast cancer treated with breast conservation method. Some varieties were identified in boost irradiation dose. Separate analysis for the datails of radiotherapy planning will be followed and the outcome of treatment is needed to evaluate the process.

Regulation of Apoptosis and Cell Cycle in Irradiated Mouse Brain / 대한방사선종양학회지

PURPOSE: To investigate the regulation of apoptosis and cell cycle in mouse brain irradiation. MATERIALS AND METHODS: 8-week old male mice, C57B1/6J were given whole body gamma-radiation with a single dose of 25 Gy using Cobalt 60 irradiator. At different times 1, 2, 4, 8 and 24hr after irradiation, mice were killed and brain tissues were collected. Apoptotic cells were scored by TUNEL assay. Expression of p53, Bcl-2, and Bax and cell cycle regulating molecules; cyclins B1, D1, E and cdk2, cdk4, p34cdc2 were analysed by Western blotting. Cell cycle was analysed by Flow cytometry. RESULTS: The peak of radiation induced apoptosis is shown at 8 hour after radiation. With a single 25 Gy irradiation, the peak of apoptotic index in C57B1/6J is 24.0+/-0.25 (p<0.05) at 8 hour after radiation. Radiation upregulated the expression of p53/tubulin, Bax/tubulin, and Bcl-2/tubulin with 1.3, 1.1 and 1.45 fold increase, respectively were shown at the peak level at 8 hour after radiation. The levels of cell cycle regulating molecules after radiation are not changed significantly except cyclin D1 with 1.3 fold increase. Fractions of Go-G1, G2-M and S phase in the cell cycle does not specific changes by time. CONCLUSIONS: In mouse brain tissue, radiation induced apoptosis is particularly shown in a specific area, subependyma. These results and lack of radiation induced changes in cell cycle offer better understanding of radiation response of normal brain tissue.

The Radioprotective Effect and Mechanism of Captopril on Radiation Induced Lung Damage in Rat / 대한방사선종양학회지

PURPOSE: It was reported that Captopril (angiotensin converting enzyme inhibitor) had an effect to reduce the pneumonitis and pulmonary fibrosis induced by radiation in rat. We performed this study to investigate the radioprotective effect and mechanism of Captopril. METHODS AND MATERIALS: The comparison was made between the radiation only group and the combined Captopril and radiation group by examining histopathologic findings and immunohistochemical stains (TNFalpha and TGFbeta1) at 2 and 8 weeks after irradiation. Each group has 8 to 10 rats (Sprague-Dawley). 12.5 Gy of X-ray was irradiated to the left hemithorax in a single fraction. Captopril (50 mg/kg/d) mixed with water was given per oral and continuously from 1 week prior to irradiation up to 8th week of the experiment. RESULT: In the combined Captopril and radiation group, the histopathologic changes which were hemorrhage into alveolar space, changes of alveolar epithelium, bronchial epithelium and blood vessels, and perivascular edema were less severe than in the radisation only group at 2 weeks. At 8 weeks, the alveolar epithelial changes and perivascular edema were less prominant in the combined Captopril and radiation group. At 2 weeks, the TNFalpha expression of the combined Captopril and radiation group was markedly decreased at the alveolar epithelium (p<0.01), lymphoid tissue (p=0.06) and the macrophage of alveolar space (p<0.01) compared with the radiation only group. Furthermore the TGFbeta1 expression was significantly prominant at the alveolar epithelium (p<0.02) and the macrophage in alveolar space (p< 0.02). At 8 weeks, the expression of TNFalpha and TGFbeta1 of most sites, except TGFbeta1 of the macrophage of alveolar space (p=0.09), showed no significant difference between 2 groups. CONCLUSION: This study revealed that early lung damage induced by irradiation was reduced with the addition of Captopril in the latent and early pneumonitis phase. The expression of TNFalpha and TGFbeta1 at 2 weeks and TGFbeta1 at 8 weeks was further decreased in the combined Captopril and radiation group than the radiation only group. From these results, it may be concluded that the proinflammatoy cytokine (TNFalpha) and fibrogenic cytokine (TGFbeta1) probably play the role of the radioprotective mechanism in Captopril.

The Role of Radiotherapy in the Management of Supratentorial Low Grade Astrocytoma / 대한치료방사선과학회지

PURPOSE: To evaluate the role of radiotherapy in the management of incompletely resected supratentorial low grade astrocytoma with the analysis of the survival, the pattern of failure, and the prognostic variables affecting survival. MATERIAL AND METHODS: Between January 1990 and December 1995, fifty- one patients with supratentorial low grade astrocytoma received radiotherapy after subtotal resection(16 patients) or stereotactic biopsy(35 patients) at Asan Medical Center. External radiotherapy was done by conventional fractionation with the total dose of 4820cGy to 6000cGy(median 5580cGy) and partial brain volume. The follow-up was done from 6 to 79 months(median 48 months). RESULTS: Overall actuarial survival rate at 2 and 5 years were 83.4% and 54.8%, respectively. Progression free survival at 2 and 5 years were 67.4% and 48.7%, respectively. The significant prognostic factors affecting overall survival rate were the performance status, T stage, histologic subtype, radiation field and radiation response. The major pattern of failure was local failure, such as progressive disease and primary site recurrence in 23 patients (45.1%). Progression free survivors excluding 2 patients were physically and intellectually intact without major neurologic deficit. CONCLUSION: Although the follow-up period of this study was relatively short, overall actuarial and progression free survival rate were encouraging. Patients with good performance status, lower T stage, pilocytic subtype, patients treated with small radiation field and radiation responder showed better survival. As the local failure was the major pattern of failure, the various efforts to decrease the local failure is necessary.

Radiation Results and Survival Rate of Small Cell Lung Cancer / 대한치료방사선과학회지

PURPOSE: To improve treatment modality and results by analysis of clinical characteristics. local control, survival and resurrence rate in limited stage small cell lung cancer. METHODS AND MATERIALS : 26 patients with limited stage small cell lung cancer were treated with combined radiation and chemotherapy from Feb. 1986 to Dec. 1992 at the National Medical Center. We followed up on 21 patients (81%) , who were mostly irradiated with 4,000-5,000cGy (75% of all patients) in the results by the analysis retrospectively. Survival rate was evaluated by the Kaplan-Meier method. RESULTS: Mean survival of irradiated patients with limited small cell lung cancer was 12 months. 1-year and 2-year survival rate were 65.3% and 15.4%. Tumor response rate and median survival after combined chemotherapy and irradiation were the following ; 50% and 15 months of complete response, and 23% and 11 months of partial response respectively. Response rates by radiation dose were 66% for below 4,000cGy. 69% for between 4,000-5,000cGy and 86% for above 5,000cGy. 21 of all patients showed treatment failure(81%), which as appeared 9 of local failure.9 of distant failure and 3 of local and distant failure. CONCLUSION: Local response rate after induction chemotherapy alone in limited stage of small cell lung cancer was 54%. Furthermore it was increased to 73% after adding of radiation. We have to increase radiation dose above 5,000cGy and need to try new effective chemotherapy agents for the improvement of local control and survival rate and also will try concurrent chemoradiotherapy in near time.

Local Control and Survival in Radiation Treatment of Locally Advanced Non-Small Cell Lung Cancer / 대한치료방사선과학회지

The retrospective analysis was performed on 37 patients with stage III non small cell lung cancer who received the radiotherapy from Feb. 1986 to Dec. 1990 at the Dept. of Radiation Oncology, National Medical Center. This analysis, with 29 patients (78.4%) having been followed from 10 to 60 months, was done to know the survival rate and significant prognostic factor. The actuarial 2, 5-year survival rates were 20.6%, 6.9% in our all patients and Median survival time was 10 months. Of patients with KPS(Karnofsky performance status) greater than 80%, the 2, 5 year survival rate and median survival time were 29.2%, 9.7% and 13 months, respectively. The 2-year survival rate and median survival time of patients with KPS less than 80% were 13.7% and 7 months, respectively. The survival difference according to performance status was statistically significant(29.2% vs. 13.7%)(p0.1). Of the prognostic factors, the difference of survival rate by initial performance status was statistically significant (p<0.05). But the difference of survival rates by pathologic cell type, stage, total radiation dose, radiotherapy response, and combination with chemotherapy were not statistically significant.

Granulocytic Sarcoma: Results of Radiotherapy / 대한치료방사선과학회지

We analyzed retrospectively the patients of granulocytic sarcoma treated with radiotherapy at the Department of Radiation Oncology, Yonsei University College of Medicine from Mar. 1987 to Mar. 1992 in an attempt to review our experience with irradiation of granulocytic sarcoma and to evaluate the treatment results for the radiation dose response. Fourteen lesions of granulocytic sarcoma in 9 patients were developed in variable clinical settings such as AML, CML and without leukemia. The involved lesions were bone, lymph node, soft tissue and skin in descending order of occurrence. All of the lesions in 9 patients were treated with external beam radiotherapy(Co-60 or electron beam). Both age distribution and clinical settings did not show any correlation with the response to treatment. The response to treatment seemed to be bettor for lesions in the bone than in other involved lesions. The majority received local irradiation of a total dose of more than 2000 cGy. Radiation dose of more than 2000 cGy showed excellent local control of 100% (11/11), while local control decreased to 33%, (1/3) with total dose less than 2000 cGy. In conclusion, local radiotherapy seems to be very effective for palliative or curative aim of granulocytic s and a radiation dose more than 2000 cGy is highly recommended.