Preliminary Report of the 1998~1999 Patterns of Care Study of Radiation Therapy for Esophageal Cancer in Korea / 대한방사선종양학회지

PURPOSE: For the first time, a nationwide survey in the Republic of Korea was conducted to determine the basic parameters for the treatment of esophageal cancer and to offer a solid cooperative system for the Korean Pattern of Care Study database. MATERIALS AND METHODS: During 1998~1999, biopsy-confirmed 246 esophageal cancer patients that received radiotherapy were enrolled from 23 different institutions in South Korea. Random sampling was based on power allocation method. Patient parameters and specific information regarding tumor characteristics and treatment methods were collected and registered through the web based PCS system. The data was analyzed by the use of the Chi-squared test. RESULTS: The median age of the collected patients was 62 years. The male to female ratio was about 91 to 9 with an absolute male predominance. The performance status ranged from ECOG 0 to 1 in 82.5% of the patients. Diagnostic procedures included an esophagogram (228 patients, 92.7%), endoscopy (226 patients, 91.9%), and a chest CT scan (238 patients, 96.7%). Squamous cell carcinoma was diagnosed in 96.3% of the patients; mid-thoracic esophageal cancer was most prevalent (110 patients, 44.7%) and 135 patients presented with clinical stage III disease. Fifty seven patients received radiotherapy alone and 37 patients received surgery with adjuvant postoperative radiotherapy. Half of the patients (123 patients) received chemotherapy together with RT and 70 patients (56.9%) received it as concurrent chemoradiotherapy. The most frequently used chemotherapeutic agent was a combination of cisplatin and 5-FU. Most patients received radiotherapy either with 6 MV (116 patients, 47.2%) or with 10 MV photons (87 patients, 35.4%). Radiotherapy was delivered through a conventional AP-PA field for 206 patients (83.7%) without using a CT plan and the median delivered dose was 3,600 cGy. The median total dose of postoperative radiotherapy was 5,040 cGy while for the non-operative patients the median total dose was 5,970 cGy. Thirty-four patients received intraluminal brachytherapy with high dose rate Iridium-192. Brachytherapy was delivered with a median dose of 300 cGy in each fraction and was typically delivered 3~4 times. The most frequently encountered complication during the radiotherapy treatment was esophagitis in 155 patients (63.0%). CONCLUSION: For the evaluation and treatment of esophageal cancer patients at radiation facilities in Korea, this study will provide guidelines and benchmark data for the solid cooperative systems of the Korean PCS. Although some differences were noted between institutions, there was no major difference in the treatment modalities and RT techniques.

Prognostic Factors Influencing the Result of Postoperative Radiotherapy in Endometrial Carcinoma / 대한방사선종양학회지

PURPOSE: This study was performed to determine the prognostic factors influencing relapse pattern, overall and disease-free survival in patients treated with postoperative radiotherapy for endometrial carcinoma. MATERIALS AND METHODS: The records of 54 patients with endometrial adenocarcinoma treated postoperative radiotherapy at Pusan National University Hospital between April 1992 and May 2003 were reviewed retrospectively. Median age of the patients was 55 (range 35~76). The distribution by surgical FIGO stages were 63.0% for 0Stage I, 14.8% for Stage II, 22.2% for Stage III. All patients received postoperative external radiotherapy up to 41.4~54 Gy (median: 50.4 Gy). Additional intravaginal brachytherapy was applied to 20 patients (37.0% of all). Median follow-up time was 35 months (5~115 months). Significant factors of this study: histologic grade, lymphovascular space invasion and myometrial invasion depth were scored (GLM score) and analyzed. Survival analysis was performed using Kaplan-Meier method. The log-rank test was used for univariate analysis and the Cox regression model for multivariate analysis. RESULTS: 5-year overall and disease-free survival rates were 87.7% and 87.1%, respectively. Prognostic factors related with overall and disease-free survival were histologic grade, lymphovascular space invasion and myometrial invasion according to the univariate analysis. According to the multivariate analysis, lymphovascular space invasion was associated with decreased disease-free survival. GLM score was a meaningful factor affecting overall and disease-free survival (p=0.0090, p=0.0073, respectively) and distant recurrence (p=0.0132), which was the sum of points of histologic grade, lymphovascular space invasion and myometrial invasion. Total failure rate was 11% with 6 patients. Relapse sites were 2 para-aortic lymph nodes, 2 lungs, a supraclavicular lymph node and a vagina. CONCLUSION: The prognosis in patients with endometrial carcinoma treated by postoperative radiotherapy was closely related with surgical histopathology. If further explorations confirm the system of prognostic factors in endometrial carcinoma, it will help us to predict the progression pattern and to manage.

Intratumoral Administration of Dendritic Cells Combined with Hyperthermia Induces Both Local and Systemic Antitumor Effect in Murine Tumor Models / 대한방사선종양학회지

PURPOSE: We examined whether intratumoral (i.t.) administration of dendritic cells (DCs) into a treated tumor could induce local and systemic antitumor effects in a mouse tumor model. METHODS AND MATERIALS: C57BL/6 mice were inoculated s.c. in the right and left thighs with MCA-102 fibrosarcoma cells on day 0 and on day 7, respectively. On day 7, the tumors (usually 6 mm in diameter) on the right thigh were heated by immersing the tumor-bearing leg in a circulating water bath at 43 degrees C for 30 min; thereafter, the immature DCs were i.t administered to the right thigh tumors. This immunization procedure was repeated on days 7, 14 and 21. The tumors in both the right and left thighs were measured every 7 days and the average sizes were determined by applying the following formula, tumor size=0.5 x (length+width). Cytotoxicity assay was done to determine tumor-specific cytotoxic T-lymphocyte activity. RESULTS: Hyperthermia induced apoptosis and heat shock proteins (HSPs) in tumor occurred maximally after 6 hr. For the local treated tumor, hyperthermia (HT) alone inhibited tumor growth compared with the untreated tumors (p<0.05), and furthermore, the i.t. administered DCs combined with hyperthermia (HT+DCs) additively inhibited tumor growth compared with HT alone (p<0.05). On the distant untreated tumor, HT alone significantly inhibited tumor growth (p<0.05), and also HT+DCs potently inhibited tumor growth (p<0.001); however, compared with HT alone, the difference was not statistically significant. In addition, HT+DCs induced strong cytotoxicity of the splenocytes against tumor cells compared to DCs or HT alone. CONCLUSION: HT+DCs induced apoptosis and increased the expression of HSPs, and so this induced a potent local and systemic antitumor response in tumor-bearing mice. This regimen may be beneficial for the treatment of human cancers.

Evaluation of Indoor Air Quality in a Department of Radiation Oncology Located Underground / 대한방사선종양학회지

PURPOSE: Indoor air quality (IAQ) in the radiation treatment center which is generally located underground is important to the health of hospital workers and patients treated over a long period of time. This study was conducted to measure and analyze the factors related to IAQ and subjective symptoms of sick building syndrome, and to establish the causes influencing IAQ and find a solution to the problems. METHODS AND MATERIALS: Self administrated questionnaire was conducted to check the workers' symptoms and understanding of the work environment. Based on a preliminary investigation, the factors related to IAQ such as temperature, humidity, fine particulate. carbon dioxide, carbon monoxide, formaldehyde, total volatile organic compounds (TVOC), and radon gas were selected and measured for a certain period of time in specific sites where hospital workers stay long in a day. And we also evaluated the surrounding environment and the efficiency of the ventilating system simultaneously, and measured the same factors at the first floor (outdoor) to compare with outdoor air quality. All collected data were assessed by the recommended standard for IAQ of the domestic and international environmental organizations. RESULTS: Hospital workers were discontented with foul odors, humidity and particulate. They complained symptoms related to musculo-skeletal system, neurologic system, and mucosal-irritatation. Most of the factors were not greater than the recommended standard, but the level of TVOC was third or fourth times as much as the measuring level of some offices in the United States. The frequency and the amount of the ventilating system were adequate, however, the problem arising in the position of outdoor-air inlets and indoor-air outlets involved a risk of the indraft of contaminated air. A careful attention was a requirement in handling and keeping chemical substances including a developing solution which has a risk of TVOC emissions, and repositioning the ventilating system was needed to solve the contaminated-air circulation immediately. CONCLUSION: We verified that some IAQ-related factors and inadequate ventilating system could cause subjective symptoms in hospital workers. The evaluation of IAQ was surely needed to improve the underground working environments for hospital workers and patients. On the basis of these data, from now on, we should actively engage in designs of the department of radiation oncology or improvement in environments of the existing facilities.

Comparison between or =60 Gy Once-Daily Thoracic Irradiation for Patients with Limited-stage Smallcell Lung Cancer

PURPOSE: To review the treatment outcomes of patients with limited-stage small-cell lung cancer (LS-SCLC) receiving daily thoracic irradiation (RT) to > or = 60 Gy. Materials and M ethods: The records of patients treated with RT for LS-SCLC between 1990 and 2002 at Pusan National University Hospital were retrospectively reviewed. Fifty-six patients were identified who had received once-daily 1.8~2 Gy fractions from 40 Gy to 63 Gy. All patients received sequential chemotherapy and then RT. These patients were arbitrary divided two groups according to thoracic radiation dose, or =60 Gy. The time to death was assessed using actuarial method. RESULTS: Two- and 5-year overall survival rates for or =60 Gy group was 32% and 41% and 14% and 21%, respectively (p=1.6). Median overall survival for or =60 Gy group was 17 and 20 months, respectively. Two case of acute Grade 3 esophagitis and one case of acute Grade 4 pneumonitis developed in > or =60 Gy group. The first relapse sites of chest for or =60 Gy group were 9/15 (60%) and 3/8 (38%), respectively (p=0.4). CONCLUSION: > or =60 Gy once-daily thoracic radiotherapy was generally well tolerated and moderately improves local control compared to <60 Gy in patients with LS_ SCLC who are treated with combination chemotherapy

The Expression of Hypoxia Inducible Factor-1alpha by Desferrioxamine Induces Radioresistance in Mouse Hepatoma Cell Line / 대한방사선종양학회지

PURPOSE: It is well known that the radiosensitivity of tumor cells can be significantly reduced under hypoxic conditions. Hypoxia-inducible factor-1alpha (HIF-1alpha) plays a pivotal role in the essential adaptive responses to hypoxia. Therefore this study investigated the relationship between HIF-1alpha expression and radiosensitivity. MATERIALS AND METHODS: Mouse hepatoma cell line hepa1c1c7 and HIF-1beta-deficient mutant cell line hepa1C4 were used to analyze the role of HIF-1alpha on radiosensitivity. These cells were exposed for 6 h to desferrioxamine (DFX) before radiation. HIF-1alpha expression was examined by Western blot. Apoptosis was assessed by DNA fragmentation, propidium iodide staining, and apoptotic cell death detection ELISA kit. Radiation sensitivity was determined using MTT assay. The radiobiological parameters, surviving fractions at 2 Gy and 8 Gy, and mean inactivation dose (MID) from the linear-quadratic model were used to assess radiation sensitivity in the statistical analyses. RESULTS: The expression of HIF-1alpha was increased, whereas apoptosis was decreased, by radiation in the presence of DFX in hepa1c1c7, but not in hepa1C4. The radiosensitivity of hepa1C4 cells was not significantly affected by DFX treatment. The radiosensitivity of hepa1c1c7 cells was significantly decreased in the presence of DFX CONCLUSION: The expression of HIF-1alpha by hypoxia-mimic agent DFX reduced apoptosis and radiosensitivity in mouse hepatoma cell line hepa1c1c7. These results suggested that HIF-1alpha could be induced by irradiation in hypoxic cells of tumor masses, and that this might increase radioresistance in hypoxic cells.

The Role of Primary Radiotherapy for Squamous Cell Carcinoma of the Supraglottic Larynx / 대한방사선종양학회지

BACKGROUND: First of all, this study was performed to assess the result of curative radiotherapy and to evaluate different possible prognostic factors for squamous cell carcinoma of the supraglottic larynx treated at the Pusan National University Hospital. The second goal of this study was by comparing our data with those of other study groups, to determine the better treatment policy of supraglottic cancer in future. METHODS AND MATERIALS: Thirty-two patients with squamous cell carcinoma of the supraglottic larynx were treated with radiotherapy at Pusan National University Hospital, from August 1985 to December 1996. Minimum follow-up period was 29 months. Twenty-seven patients (84.4%) were followed up over 5 years. Radiotherapy was delivered with 6 MV photons to the primary laryngeal tumor and regional lymphatics with shrinking field technique. All patients received radiotherapy under conventional fractionated schedule (once a day). Median total tumor dose was 70.2 Gy (range, 55.8 to 75.6 Gy) on primary or gross tumor lesion. Thirteen patients had induction chemotherapy with cisplatin and 5-fluorouracil (1-3 cycles). Patient distribution, according to the different stages, were as follows: stage I, 5/32 (15.6%); stage II, 10/32 (31.3%); stage III, 8/32 (25%); stage IV, 9/32 (28.1%). RESULTS: The 5-year overall survival rate of the whole series (32 patients) was 51.7%. The overall survival rate at 5-years was 80% in stage I, 66.7% in stage II, 42.9% in stage III, 25% in stage IV ( p= 0.0958). The 5-year local control rates after radiotherapy were as follows: stage I, 100%; stage II, 60%; stage III, 62.5%; stage IV, 44.4% ( p=0.233). Overall vocal preservation rates was 65.6%, 100% in stage I, 70% in stage II, 62.5% in stage III, 44.4% in stage IV ( p=0.210). There was no statistical significance in survival and local control rate between neoadjuvant chemotherapy followed by radiotherapy group and radiotherapy alone group. Severe laryngeal edema was found in 2 cases after radiotherapy, emergent tracheostomy was done. Four patients were died from distant metastsis, : three in lung, one in brain. Double primary tumor was found in 2 cases, one in lung (metachronous), another in thyroid (synchronous). Ulcerative lesions were revealed as unfavorable prognostic factor ( p=0.0215), and radiation dose (more or less than 70.2 Gy) was an important factor on survival ( p=0.0302). CONCLUSIONS: The role of radiotherapy in the treatment of supraglottic carcinoma is to improve the survival and to preserve the laryngeal function. Based on our data and other studies, early and moderately advanced supraglottic carcinomas could be successfully treated with either conservative surgery or radiotherapy alone. Both modalities showed similar results in survival and vocal preservation. For the advanced cases, radiotherapy alone is inadequate for curative aim and surgery combined with radiotherapy should be done in operable patients. When patients refuse operation or want to preserve vocal function, or for the patients with inoperable medical conditions, combined chemoradiotherapy (concurrent) or altered fractionated radiotherapy with or without radiosensitizer should be taken into consideration in future.

Local Control after Radiation Therapy for T1-T2 Glottic Carcinoma / 대한치료방사선과학회지

PURPOSE: To assess the effectiveness and problems of the primary radiation therapy and salvage surgery in a series of patients affected by T1-T2 NO glottic cancers treated from 1985 to 1991 at the Pusan National University Hospital. MATERIALS AND METHODS: From 8.85 to 12/91, 34 patients affected by early glottic carcinoma histologically proven were treated with curative radiation therapy. Distribution of patients according to T stage was 30 for T1 and 4 T2. Male to female ratio was 33:1. Age of patients ranged from 31 to 73 with mean age of 58 years. All of the patients were treated with radical radiation with total tumor dose of 63-75. 3 Gy(median 68.2 Gy), of 5 weekly fractions of 1.8-2Gy and with 6MV photon beams through two laterally opposed fields. RESULTS: The overall 5-year local control rates were 74%(8/30) for T1, and 25%(3/4) for T2. The main cause of failure was progression or recurrence in T(10/11). One failures were observed in T and N at the same time. Of these 11 patients, 9(81%) were salvaged with surgery. After surgical salvage of radiation failures, the 5-year survival rates were 96% for T1 and 75% T2. Among the survivors, 73% of T1 and 33% of T2 were able to preserve the larynx. CONCLUSION: It can be concluded that radiotherapy is the first choice in the treatment of glottic T1 carcinoma.