VEGF as a Predictor for Response to Definitive Chemoradiotherapy and COX-2 as a Prognosticator for Survival in Esophageal Squamous Cell Carcinoma

We investigated the patterns of pretreatment expression of the epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2) by immunohistochemical staining and determined their correlation with treatment response and survival in 44 patients with esophageal squamous cell carcinoma (ESCC) treated with definitive concurrent chemoradiotherapy (CCRT). The definitive CCRT consisted of a median dose of 54 Gy (range: 40.0-68.4 Gy) and two cycles of concurrent administration of mostly 5-fluorouracil + cisplatinum. High expression of EGFR, VEGF, and COX-2 was found in 79.5%, 31.8%, and 38.6%, respectively. The Cox regression analysis for overall survival (OS) showed that both the treatment response and COX-2 expression were significant. The 3-yr OS rates of patients that achieved a complete response and those that did not were 46.7% and 5.3%, respectively (P = 0.006). The logistic regression analysis for treatment response with various parameters showed that only a high expression of VEGF was significantly associated with a complete response. Unlike other well-known studies, higher expression of VEGF was significantly correlated with a complete response to CCRT in this study. However, higher expression of COX-2 was significantly associated with shorter survival. These results suggest that VEGF might be a predictive factor for treatment response and COX-2 a prognostic factor for OS in patients with ESCC after definitive CCRT.

Analysis on the Calculated Dose in the Lung Radiation Surgery Planning Using TomoTherpay / 의학물리

The applicability and feasibility of TomoTherapy in the lung radiation surgery was analyzed by comparison of the calculated dose distribution in TomoTherapy planning with the results of conventional IMRS (intensity modulated radiation surgery) using LINAC (linear accelerator). The acquired CT (computed tomograph) images of total 10 patients whose tumors' motion were less than 5 mm were used in the radiation surgery planning and the same prescribed dose and the same dose constraints were used between TomoTherapy and LINAC. The results of TomoTherapy planning fulfilled the dose requirement in GTV (gross tumor volume) and OAR (organ at risk) in the same with the conventional IMRS using LINAC. TomoTherapy was superior in the view point of low dose in the normal lung tissue and conventional LINAC was superior in the dose homogeneity in GTV. The calculated time for treatment beam delivery was long more than two times in TomoTherapy compared with the conventional LINAC. Based on the results in this study, TomoTherapy can be evaluated as an effective way of lung radiation surgery for the patients whose tumor motion is little when the optimal planning is produced considering patient's condition and suitability of dose distribution.

The Results of Curative Concurrent Chemoradiotherapy for Anal Carcinoma / 대한방사선종양학회지

PURPOSE: To evaluate the predictive factors for treatment response and prognostic factors affecting survival outcomes after concurrent chemoradiotherapy (CCRT) for patients with anal squamous cell carcinoma. MATERIALS AND METHODS: Medical records of forty two patients with histologically confirmed analsquamous cell carcinoma, who had complete CCRT between 1993 and 2008, were reviewed retrospectively. Median age was 61.5 years (39~89 years), and median radiotherapy (RT) dose was 50.4 Gy (30.0~64.0 Gy). A total of 36 patients had equal to or less than T2 stage (85.7%). Fourteen patients (33.3%) showed regional nodal metastasis, 36 patients (85.7%) were treated with 5-fluorouracil (5-FU) plus mitomycin, and the remaining patients were treated by 5-FU plus cisplatinum. RESULTS: The median follow-up time was 62 months (2~202 months).The 5-year overall survival, locoregional relapse-free survival, disease-free survival, and colostomy-free survival rates were 86.0%, 71.7%, 71.7%, 78.2%, respectively. Regarding overall survival, the Eastern Cooperative Oncology Group (ECOG) performance status and complete response were found to be significant prognostic factors on univariate analysis. For multivariate analysis, only the ECOG performance status was significant. No significant factor was found for locoregional relapse-free survival or disease-free survival and similarly for treatment response, no significant factor was determined on logistic regression analysis. There were 7 patients who had local or regional recurrences and one patient with distant metastasis. The only evaluable toxicity in all patients was radiation dermatitis of perianal skin (grade 3), which developed in 4 patients (9.5%) and grade 2 in 22 patients (52.4%). CONCLUSION: This study revealed that patients with a performance score of ECOG 0-1 survived significantly longer than those with a poorer score. Finally, there was no significant predicting factors tested for treatment response.

Analysis on the Effect of Field Width in the Delineation of Planning Target Volume for TomoTherapy / 의학물리

The Hi-Art system for TomoTherapy allows only three (1.0 cm, 2.5 cm, 5.0 cm) field widths and this can produce different dose distribution around the end of PTV (Planning target volume) in the direction of jaw movement. In this study, we investigated the effect of field width on the dose difference around the PTV using DQA (Delivery quality assurance) phantom and real clinical patient cases. In the analysis with DQA phantom, the calculated dose and irradiated films showed that the more dose was widely spreaded out in the end region of PTV as increase of field width. The 2.5 cm field width showed a 1.6 cm wider dose profile and the 5.0 cm field width showed a 4.2 cm wider dose profile compared with the 1.0 cm field width in the region of 50% of maximum dose. The analysis with four patient cases also showed the similar results with the DQA phantom which means that more dose was irradiated around the superior and inferior end of PTV as an increase of field width. The 5.0 cm field width produced the remarkable high dose distribution around the end region of PTV and we could evaluate the effect quantitatively with the calculation of DVH (Dose volume histogram) of the virtual PTVs which were delineated around the end of PTV in the direction of jaw variation. From these results, we could verify that the margin for PTV in the direction of table movement should be reduced compared with the conventional margin for PTV when the large field such as 5.0 cm was used in TomoTherapy.

A Retrospective Study of the Radiotherapy Care Patterns for Patients with Laryngeal Cancer and Comparison of Different Korean Hospitals Treated from 1998 through 1999 / 대한방사선종양학회지

PURPOSE: To investigate the care patterns for radiation therapy and to determine inter-hospital differences for patients with laryngeal carcinoma in Korea. MATERIALS AND METHODS: A total of 237 cases of laryngeal carcinoma (glottis, 144; supraglottis, 93) assembled from 23 hospitals, who underwent irradiation in the year of 1998 and 1999, were retrospectively analyzed to investigate inter-hospital differences with respect to radiotherapy treatment. We grouped the 23 hospitals based on the number of new patients annually irradiated in 1998; and designated them as group A (> or =900 patients), group B (> or =400 patients and <900 patients), and group C (<400 patients). RESULTS: The median age of the 237 patients was 62 years (range, 25 to 88 years), of which 216 were male and 21 were female. The clinical stages were distributed as follows: for glottis cancer, I; 61.8%, II; 21.5%, III; 4.2%, IVa; 11.1%, IVb; 1.4%, and in supraglottic cancer, I; 4.3%, II; 19.4%, III; 28.0%, IVa; 43.0%, IVb; 5.4%, respectively. Some differences were observed among the 3 groups with respect to the dose calculation method, radiation energy, field arrangement, and use of an immobilization device. No significant difference among 3 hospital groups was observed with respect to treatment modality, irradiation volume, and median total dose delivered to the primary site. CONCLUSION: This study revealed that radiotherapy process and patterns of care are relatively uniform in laryngeal cancer patients in Korean hospitals, and we hope this nationwide data can be used as a basis for the standardization of radiotherapy for the treatment of laryngeal cancer.

Analysis on the Decrease of Planning Target Volume in the Case of Lung Radiation Surgery with the Application of Respiratory Gated Radiotherpy Method / 의학물리

The application of a respiratory gated radiotherpy method to the lung radiation surgery was evaluated compared with the conventional method in which the whole tumor motion range is considered in the delineation of PTV (Planning target volume). The four dimensional CT simulation images were acquired for the five NSCLC (Non-small cell lung cancer) patients for radiation surgery. The respiratory gated plan was prepared with the 50% phase CT images and the conventional method was planned based on the ITV (Internal target volume) which include all the target volumes created in each phase CT images within a whole respiratory period. The DVH (Dose volume histogram) of OAR (Organ at risk) which calculated in each method was compared for the evaluation of the plan properness. The relative decrease of OARs' DVH were verified in the application of respiratory gated method. The average decrease rate were 16.88+/-9.97% in the bronchus, 34.13+/-19.15% in the spinal cord, 28.42+/-18.49% in the chest wall and 32.48+/-16.66% in the lung. Based on these results, we can verified the applicability and the effectiveness of the respiratory gated method in the lung radiation surgery.

Results of Preoperative Concurrent Chemoradiotherapy for the Treatment of Rectal Cancer / 대한방사선종양학회지

PURPOSE: The purpose of this study is to evaluate anal sphincter preservation rates, survival rates, and prognostic factors in patients with rectal cancer treated with preoperative chemoradiotherapy. MATERIALS AND METHODS: One hundred fifty patients with pathologic confirmed rectal cancer and treated by preoperative chemoradiotherapy between January 1999 and June 2007. Of the 150 patients, the 82 who completed the scheduled chemoradiotherapy, received definitive surgery at our hospital, and did not have distant metastasis upon initial diagnosis were enrolled in this study. The radiation dose delivered to the whole pelvis ranged from 41.4 to 46.0 Gy (median 44.0 Gy) using daily fractions of 1.8~2.0 Gy at 5 days per week and a boost dose to the primary tumor and high risk area up to a total of 43.2~54 Gy (median 50.4 Gy). Sixty patients (80.5%) received 5-fluorouracil, leucovorin, and cisplatin, while 16 patients (19.5%) were administered 5-fluorouracil and leucovorin every 4 weeks concurrently during radiotherapy. Surgery was performed for 3 to 45 weeks (median 7 weeks) after completion of chemoradiotherapy. RESULTS: The sphincter preservation rates for all patients were 73.2% (60/82). Of the 48 patients whose tumor was located at less than 5 cm away from the anal verge, 31 (64.6%) underwent sphincter-saving surgery. Moreover, of the 34 patients whose tumor was located at greater than or equal to 5 cm away from the anal verge, 29 (85.3%) were able to preserve their anal sphincter. A pathologic complete response was achieved in 14.6% (12/82) of all patients. The downstaging rates were 42.7% (35/82) for the T stage, 75.5% (37/49) for the N stage, and 67.1% (55/82) for the overall stages. The median follow-up period was 38 months (range 11~107 months). The overall 5-year survival, disease-free survival, and locoregional control rates were 67.4%, 58.9% and 84.4%, respectively. The 5-year overall survival rates based on the pathologic stage were 100% for stage 0 (n=12), 59.1% for stage I (n=16), 78.6% for stage II (n=30), 36.9% for stage III (n=23), and one patient with pathologic stage IV was alive for 43 months (p=0.02). The 5-year disease-free survival rates were 77.8% for stage 0, 63.6% for stage I, 58.9% for stage II, 51.1% for stage III, and 0% for stage IV (p55), clinical stage (I+II vs. III), radiotherapy to surgery interval (6 weeks), operation type (sphincter preservation vs. no preservation), pathologic T stage, pathologic N stage, pathologic overall stage (0 vs. I+II vs. III+IV), and pathologic response (complete vs. non-CR), only age and pathologic N stage were significant predictors of overall survival, pathologic overall stage for disease-free survival, and pathologic N stage for locoregional control rates, respectively. Recurrence was observed in 25 patients (local recurrence in 10 patients, distant metastasis in 13 patients, and both in 2 patients). Acute hematologic toxicity (> or =grade 3) during chemoradiotherapy was observed in 2 patients, while skin toxicity was observed in 1 patient. Complications developing within 60 days after surgery and required admission or surgical intervention, were observed in 11 patients: anastomotic leakage in 5 patients, pelvic abscess in 2 patients, and others in 4 patients. CONCLUSION: Preoperative chemoradiotherapy was an effective modality to achieve downstaging and sphincter preservation in rectal cancer cases with a relatively low toxicity. Pathologic N stage was a statistically significant prognostic factor for survival and locoregional control and so, more intensified postoperative adjuvant chemotherapy should be considered in these patients.

MDM2, p53 and pRb Expression Prior to Definitive Chemoradiotherapy in Esophageal Carcinoma / 대한방사선종양학회지

PURPOSE: This study evaluated the pretreatment expression patterns of MDM2, p53, and pRb proteins to determine if the expression patterns could predict the outcome of concurrent chemoradiotherapy (CCRT) for esophageal squamous cell carcinoma and aid in the decisions for the selection of treatment modalities. MATERIALS AND METHODS: Fifty-one patients that were treated with definitive chemoradiotherapy for stage I~IVa esophageal squamous cell carcinoma were selected for this study. Radiotherapy was administered with daily 1.8~2 Gy fractions up to a median dose of 54 Gy for primary tumors, and with four cycles of cisplatin/5- fluorouracil chemotherapy that was administered every 4 weeks, the first two cycles of which were administered concurrently with radiotherapy. Expression of MDM2, p53, and pRb was investigated by immunohistochemical analysis using pretreatment biopsy specimens. RESULTS: MDM2, p53, and pRb were detected with high immunoreactivity in 19.6%, 27.5%, and 66.7% of the patients, respectively. However, there was no significant correlation between expression of these factors and clinical outcome. By the use of multivariate analysis with nine covariates-age, tumor location, tumor length, stage, pathological response, clinical response, MDM2 expression, p53 expression, and pRb expression, only pathological response and stage were significant factors for cause-specific survival. CONCLUSION: Expression of MDM2, p53, and pRb was not found to be clinically significant for predicting outcomes after CCRT in this study. Further studies with a larger patient population and longer follow-up periods are needed to re-evaluate the expression pattern and to identify new predictors for CCRT response.

Treatments Results and Prognostic Factors in Locally Advanced Hypopharyngeal Cancer / 대한방사선종양학회지

PURPOSE: The purpose of this study is to present the treatment results and to identify possible prognostic indicators in patients with locally advanced hypopharyngeal carcinoma. MATERIALS AND METHODS: Between October 1985 to December 2000, 90 patients who had locally advanced stage IV hypopharyngeal carcinoma were studied retrospectively. Twelve patients were treated with radiotherapy alone, 65 patients were treated with a combination of chemotherapy and radiotherapy, and 13 patients were treated with surgery and postoperative radiotherapy with or without neoadjuvant chemotherapy. Total radiation dose ranged from 59.0 to 88.2 Gy (median 70 Gy) for radiotherpay alone. Most patients had ciplatin and 5-fluorouracil, and others had cisplatin and pepleomycin or vincristin. Median follow-up period was 15 months. Kaplan-Meier method was used for survival rate and Cox proportional hazard model for multivariate analysis of prognostic factors. RESULTS: Overall 3- and 5-year survival rates were 27% and 17%, respectively. The 2-year locoregional control rates were 33% for radiotherapy alone, 32% for combined chemotherapy and radiotherapy, and 81% for combined surgery and radiotherapy (p=0.006). The prognostic factors affecting overall survival were T stage, concurrent chemoradiation and treatment response. Overall 3- and 5-year laryngeal preservation rates in combined chemotherapy and radiotherapy were 26% and 22%, respectively. Of these, the 5-year laryngeal preservation rates were 52% for concurrent chemoradiation group (n=11), and 16% for neoadjuvant chemotherapy and radiotherapy (n=54, p=0.012). CONCLUSION: Surgery and postoperative radiotherapy showed better results than radiotherapy alone or with chemotherapy. Radiotherapy combined with concurrent chemotherapy is an effective modality to achieve organ preservation in locally advanced hypopharyngeal cancer. Further prospective randomized studies will be required.

Analysis of Respiratory Motional Effect on the Cone-beam CT Image / 의학물리

The cone-beam CT (CBCT) which is acquired using on-board imager (OBI) attached to a linear accelerator is widely used for the image guided radiation therapy. In this study, the effect of respiratory motion on the quality of CBCT image was evaluated. A phantom system was constructed in order to simulate respiratory motion. One part of the system is composed of a moving plate and a motor driving component which can control the motional cycle and motional range. The other part is solid water phantom containing a small cubic phantom (2 x 2 x 2 cm3) surrounded by air which simulate a small tumor volume in the lung air cavity. CBCT images of the phantom were acquired in 20 different cases and compared with the image in the static status. The 20 different cases are constituted with 4 different motional ranges (0.7 cm, 1.6 cm, 2.4 cm, 3.1 cm) and 5 different motional cycles (2, 3, 4, 5, 6 sec). The difference of CT number in the coronal image was evaluated as a deformation degree of image quality. The relative average pixel intensity values as a compared CT number of static CBCT image were 71.07% at 0.7 cm motional range, 48.88% at 1.6 cm motional range, 30.60% at 2.4 cm motional range, 17.38% at 3.1 cm motional range. The tumor phantom sizes which were defined as the length with different CT number compared with air were increased as the increase of motional range (2.1 cm: no motion, 2.66 cm: 0.7 cm motion, 3.06 cm: 1.6 cm motion, 3.62 cm: 2.4 cm motion, 4.04 cm: 3.1 cm motion). This study shows that respiratory motion in the region of inhomogeneous structures can degrade the image quality of CBCT and it must be considered in the process of setup error correction using CBCT images.

Thoracic Radiotherapy Combined with Chemotherapy in Patients with Limited-stage Small-cell Lung Cancer

PURPOSE : We evaluated the optimal combination of thoracic radiotherapy with chemotherapy in patients with limited-stage small cell lung cancer (L-SCLC). MATERIALS AND METHODS : We retrospectively analyzed the data of 95 patients with L-SCLC who completed the planned thoracic radiotherapy combined with chemotherapy between January 1998 and March 2004. Thoracic radiotherapy was done with conventional fractionation to the median dose of 60Gy. Radiotherapy was combined with chemotherapy concurrently (n=67), alternating (n=19), or sequentially (n=9). Chemotherapy consisted of EP or EC (etoposide 100 mg/m2, cisplatin 60 mg/m2 or carboplatin 5~6xAUC ). The median cycle of chemotherapy was 6 with the range of 2 to 8. RESULTS : The median survival of all 95 patients was 20 months and 2-, 3-, and 5-year overall survival rate was 39%, 26%, and 19%, respectively. Radiation dose above 55 Gy did not show better survival result than dose below 55 Gy (p=0.59). The median survival and 5-year survival rate of 67 patients with concurrent chemoradiation was 23 months and 24% while those of 28 patients with alternating or sequential chemoradiation was 16 months and 8%, respectively (p=0.007). Concurrent thoracic radiotherapy combined after 2 cycles of chemotherapy showed the best survival results among the combination methods (p=0.29). The survival was improved in patients with chemotherapy more than 5 cycles comparing to patients with less than 5 (p=0.03). Patients with PCI showed the median survival of 43 months and 5-year survival rate of 35% vs. 18 months and 16% in patients without PCI, respectively (p=0.02). In multivariate analysis, the concurrent chemoradiation was the only significant prognostic factor affecting to the survival. CONCLUSION : Concurrent chemoradiation after 2 cycles of chemotherapy showed the best survival results in our study group. Full dose of chemotherapy to 6 cycles needed to be proceeded in tolerable patients. PCI can be recommended to the patients with complete response after chemoradiation

Results of Curative Radiation Therapy with or without Chemotherapy for Stage III Unresectable Non-Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We retrospectively analyzed the patients who received curative radiotherapy for unresectable stage III NSCLC to investigate the impact of chemotherapy. MATERIALS AND METHODS: From 1998 to 2001, the records of 224 patients who completed curative radiotherapy for NSCLC were reviewed. There were 210 males and 14 females, and their median age was 64 years (range 38 ~83). 54 patients had stage IIIA disease and 170 patients had stage IIIB disease. Conventional radiotherapy was given and the radiation dose ranged from 50~70 Gy with a median of 60 Gy, and chemotherapy was combined for 116 patients (52%). RESULTS: The median survival, the 2-year, and 5-year actuarial survival rates of all 224 patients were 15 months, 30%, and 7%, respectively. The median survival of the patients with stage IIIA and IIIB disease were 21 months and 13 months, respectively (p=0.14). The median survival of patients who received chemoradiation was 18 months compared to 14 months for the patients who received RT alone (p=0.02). Among the chemoradiation group of patients, the median survival time of the patients who received 1 to 3 cycles of chemotherapy was 16 months and that for the patients who received more than 3 cycles was 22 months (p=0.07). We evaluated the effects of the timing of chemoradiation in 57 patients who received more than 3 cycles of chemotherapy. The median survival of the patients with the concurrent sequence was 25 months and that for the patients with the sequential chemotherapy was 19 months (p=0.81). CONCLUSIONS: For advanced stage III non-small cell lung cancer patients who completed the curative radiotherapy, the addition of chemotherapy improved the survival compared to the patients who received radiotherapy alone.

Assessment of Tumor Regression by Consecutive Pelvic Magnetic Resonance Imaging and Dose Modification during High- Dose-Rate Brachytherapy for Carcinoma of the Uterine Cervix / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To assess tumor regression, as determined by pelvic magnetic resonance imaging (MRI), and evaluate the efficacies and toxicities of the interim brachytherapy (BT) modification method, according to tumor regression during multi-fractionated high-dose-rate (HDR) BT for uterine cervical cancer. MATERIALS AND METHODS: Consecutive MRI studies were performed pre-radiotherapy (RT), pre-BT and during interfraction of BT (inter-BT) in 69 patients with cervical cancer. External beam radiotherapy (EBRT) was performed, using a 10 MV X-ray, in daily fraction of 1.8 Gy with 4-fields, 5 d/wk. Radiation was delivered up to 50.4 Gy, with midline shielding at around 30.6 Gy. Of all 69 patients, 50 received modified interim BT after checking the inter-BT MRI. The BT was delivered in two sessions; the first was composed of several 5 Gy fractions to point A, twice weekly, using three channel applicators. According to the three measured orthogonal diameters of the regressed tumor, based on inter-BT MR images, the initial BT plan was modified, with the second session consisting of a few fractions of less than 5 Gy to point A, using a cervical cylinder applicator. RESULTS: The numbers of patients in FIGO stages Ib, IIa, IIb and IIIb+IVa were 19 (27.5%), 18 (26.1%), 27 (39.2%) and 5 (7.2%), respectively. Our treatment characteristics were comparable to those from the literatures with respect to the biologically effective dose (BED) to point A, rectum and bladder as reference points. In the regression analysis a significant correlation was observed between tumor regression and the cumulative dose to point A on the follow-up MRI. Nearly 80% regression of the initial tumor volume occurred after 30.6 Gy of EBRT, and this increased to 90% after an additional 25 Gy in 5 fractions of BT, which corresponds to 73.6 Gy of cumulative BED10 to point A. The median total fraction number, and those at the first and second sessions of BT were 8 (5~10), 5 (3~7) and 3 (1~5), respectively. The median follow-up time was 53 months (range, 9~66 months). The 4-year disease-free survival rate of all patients was 86.8%. Six (8.7%) patients developed pelvic failures, but major late complications developed in only two (2.9%). CONCLUSION: Our study shows that effective tumor control, equivalent survival and low rates of major complications can be achieved by modifying the fraction size during BT according to tumor regression, as determined by consecutive MR images. We recommend checking the follow-up MRI at a cumulative BED10 of around 65 Gy to point A, with the initial BT modified at a final booster BT session.

The Analysis of a Cerrobend Compensator and a Electronic Compensator Designed by a Radiation Treatment Planning System / 의학물리

In this study, the physical compensator made with the high density material, Cerrobend, and the electronic compensator realized by the movement of a dynamic multileaf collimator were analyzed in order to verify the properness of a design function in the commercial RTP (radiation treatment planning) system, Eclipse. The CT images of a phantom composed of the regions of five different thickness were acquired and the proper compensator which can make homogeneous dose distribution at the reference depth was designed in the RTP. The frame for the casting of Cerrobend compensator was made with a computerized automatic styrofoam cutting device and the Millennium MLC-120 was used for the electronic compensator. All the dose values and isodose distributions were measured with a radiographic EDR2 film. The deviation of a dose distribution was +/-0.99 cGy and +/-1.82 cGy in each case of a Cerrobend compensator and a electronic compensator compared with a +/-13.93 cGy deviation in an open beam condition. Which showed the proper function of the designed compensators in the view point of a homogeneous dose distribution. When the absolute dose value was analyzed, the Cerrobend compensator showed a +3.83% error and the electronic compensator showed a -4.37% error in comparison with a dose value which was calculated in the RTP. These errors can be admtted as an reasonable results that approve the accuracy of the compensator design in the RTP considering the error in the process of the manufacturing of the Cerrobend compensator and the limitation of a film in the absolute dosimetry.

Postmastectomy Radiotherapy and Chemotherapy in Patients with Breast Cancer / 대한방사선종양학회지

PURPOSE: To evaluate the treatment outcomes after postmastectomy radiotherapy (PMRT) and chemotherapy in patients with breast cancer. MATERIALS AND METHODS: The PMRT were retrospectively analyzed in 83 patients with stage II-III female breast cancer treated between 1989 and 1995. The median age was 46 years (range, 23-77); Seventy- seven patients had modified radical mastectomies, 5 radical mastectomies and 1 simple mastectomy. Three patients (4%) had pathologically negative axillae, and the remaining 80 (96%) had positive axillae. Eleven, 23, 44 and 5 patients had pathological stages IIA, IIB, IIIA, and IIIB, retrospectively. Eighty (96%) patients were treated with hockey-stick fields. The median dose of PMRT was 50.4 Gy, in 1.8 Gy fractions. Adjuvant systemic chemotherapy was given to 74 patients (89%). CMF-based or doxorubicin-containing regimens were given to 54 patients (65%). The median follow-up time was 82 months (range, 8-171) after the mastectomy. RESULTS: The 5 and 10-year overall survival rates for all patients were 65 and 49%, respectively. The univariate and multivariate analyses of the factors affecting the overall survival revealed the stage to be the most significant prognostic factor (p=0.002), followed by the combination of chemotherapy. Thirteen patients (16%) developed a LRF, at an interval of 4-84 months after radiotherapy, with a median of 20 months. The only significant prognostic factor affecting LRF was the combination of chemotherapy, in both the univariate and multivariate analyses. With respect to the sequence of chemoradiation, the sequence had no statistical significance (p=0.90). According to the time interval from mastectomy to the onset of radiotherapy, the LRFR of the patients group treated by RT within or after 6 month postmastectomy 6 months were 14 vs. 27%, respectively (p=0.24). One third of the patients (26/83) developed distant metastasis, in 2-92 months, after radiotherapy, with a median of 21 months. The most commonly involved site was bone in 13 cases. The pathological staging was the only significant prognostic factor in both the univariate and multivariate analyses that affected distant failure. Radiological findingof radiation pneumonitis on a simple chest x-ray was shown in 20% (17/83), with a time interval ranging from 2 to 7 months post-radiotherapy, with a median of 3 months. The stable lung fibrosis settled in 11 patients (65%). CONCLUSIONS: It was concluded through this analysis that the combination of PMRT with in chemotherapy resulted in better overall survival and local control than PMRT alone in patients needing PMRT.

RESULTS of Concurrent Chemoradiotherapy and Intraluminal Brachytherapy in Esophageal Carcinoma: Retrospective Analysis with Respect to Survival / 대한방사선종양학회지

PURPOSE: To evaluate the efficacies and toxicities of concurrent chemoradiotherapy (CCRT), with or without intraluminal brachytherapy (ILB), using a retrospective analysis in esophageal carcinomas with respect to survival. MATERIALS AND METHODS: From April 1995 to July 2001, a total of 65 patients, diagnosed with an esophageal carcinoma, were treated by CCRT, with 21 also treated by ILB after CCRT. External radiotherapy was performed using 6 or 10 MV X-rays, with a dose range of 46.8~69.6 Gy (median; 59.4). The ILB was performed using high-dose-rate brachytherapy with Ir-192. The fractionation of ILB was 3 Gy by 4, or 5 Gy by 2 fractions. Cisplatin (75 mg/m2) was given on each first day of weeks 1, 5, 9 and 13, and 5-FU (1,000 mg/m2) as a continuous infusion for the first 4 days of each course. RESULTS: The median survival time of all patients was 15 months, and the 1, 2 and 3-year survival rates were 55.4, 29.2 and 20.7%, respectively. The 2-year survival rates of the patients with and without ILB were 33.3 and 27.3%, respectively (p=0.80). The 2-year survival rates of the patients with a complete, partial and no response were 44.1, 13.8 and 0%, respectively (p=0.02). The response to treatment was the only significant factor affecting the overall survival from a multivariate analysis. CONCLUSIONS: This study has shown that the survival outcomes of CCRT were much better than previous results with radiotherapy alone. However, the addition of ILB after CCRT showed no advantage over that of CCRT alone.

Investigation of Study Items for the Patterns of Care Study in the Radiotherapy of Laryngeal Cancer: Preliminary Results / 대한방사선종양학회지

PURPOSE: In order to develop the national guide-lines for the standardization of radiotherapy we are planning to establish a web-based, on-line data-base system for laryngeal cancer. As a first step this study was performed to accumulate the basic clinical information of laryngeal cancer and to determine the items needed for the data-base system. MATERIALS AND METHODS: We analyzed the clinical data of patients who were treated under the diagnosis of laryngeal cancer from January 1998 through December 1999 in the South-west area of Korea. Eligibility criteria of the patients are as follows: 18 years or older, currently diagnosed with primary epithelial carcinoma of larynx, and no history of previous treatments for another cancers and the other laryngeal diseases. The items were developed and filled out by radiation oncologist who are members of Korean Southwest Radiation Oncology Group. SPSS v10.0 software was used for statistical analysis. RESULTS: Data of forty-five patients were collected. Age distribution of patients ranged from 28 to 88 years (median, 61). Laryngeal cancer occurred predominantly in males (10:1 sex ratio). Twenty-eight patients (62%) had primary cancers in the glottis and 17 (38%) in the supraglottis. Most of them were diagnosed pathologically as squamous cell carcinoma (44/45, 98%). Twenty-four of 28 glottic cancer patients (86%) had AJCC (American Joint Committee on Cancer) stage I/II, but 50% (8/16) had in supraglottic cancer patients (p=0.02). Most patients (89%) had the symptom of hoarseness. Indirect laryngoscopy was done in all patients and direct laryngoscopy was performed in 43 (98%) patients. Twenty-one of 28 (75%) glottic cancer cases and 6 of 17 (35%) supraglottic cancer cases were treated with radiation alone, respectively. The combined treatment of surgery and radiation was used in 5 (18%) glottic and 8 (47%) supraglottic patients. Chemotherapy and radiation was used in 2 (7%) glottic and 3 (18%) supraglottic patients. There was no statistically significant difference in the use of combined modality treatments between glottic and supraglottic cancers (p=0.20). In all patients, 6 MV X-ray was used with conventional fractionation. The fraction size was 2 Gy in 80% of glottic cancer patients compared with 1.8 Gy in 59% of the patients with supraglottic cancers. The mean total dose delivered to primary lesions were 65.98 Gy and 70.15 Gy in glottic and supraglottic patients treated, respectively, with radiation alone. Based on the collected data, 12 modules with 90 items were developed for the study of the patterns of care in laryngeal cancer. CONCLUSION: The study items for laryngeal cancer were developed. In the near future, a web system will be established based on the items investigated, and then a nation-wide analysis on laryngeal cancer will be processed for the standardization and optimization of radiotherapy.

Radiation-induced Apoptosis in Developing Fetal Rat Cerebral Cortex / 대한방사선종양학회지

PURPOSE: This study was performed to investigate apoptosis by radiation in the developing fetal rat brain. MATERIALS AND METHODS: Fetal brains were irradiated in utero between the 17th and 19th days of fetal life (E17-19) by linear accelerator. A dose of irradiation ranging from 1 Gy to 4 Gy was used to evaluate dose dependency. To test time dependency the rats were irradiated with 2 Gy and then the fetal brain specimens were removed at variable time course; 1, 3, 6, 12 and 24 hours after the onset of irradiation. Immunohistochemical staining using in situ TdT-mediated dUTP nick end labelling (TUNEL) technique was used for apoptotic cells. The cerebral cortex, including three zones of cortical zone (CZ), intermediate zone (IZ), and ventricular zone (VZ), was examined. RESULTS: TUNEL positive cells revealed typical features of apoptotic cells under light microscope in the fetal rat cerebral cortex. Apoptotic cells were not found in the cerebral cortex of non-irradiated fetal rats, but did appear in the entire cerebral cortex after 1 Gy irradiation, and were more extensive at the ventricular and intermediate zones than at the cortical zone. The extent of apoptosis was increased with increasing doses of radiation. Apoptosis reached the peak at 6 hours after the onset of 2 Gy irradiation and persisted until 24 hours. CONCLUSION: Typical morphologic features of apoptosis by irradiation were observed in the developing fetal rat cerebral cortex. It was more extensive at the ventricular and intermediate zones than at the cortical zone, which suggested that stem cells or early differentiating cells are more radiosensitive than differentiated cells of the cortical zone.

Results of Curative Radiotherapy Alone in Patients with Uterine Cervical Carcinomas / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To evaluate the role of curative radiotherapy alone in the treatment of uterine cervical carcinomas, by a retrospective analysis with respects to survival and pelvic control, and to find any risk factors of failure MATERIALS AND METHODS: Between Jan. 1990 and Dec. 1995, a total of 187 patients, diagnosed with uterine cervical carcinomas in FIGO stages greater than IA, were treated by curative radiotherapy alone with no chemotherapy. The ages of the patients ranged from 26 to 80 years, with a median of 60 years. The number of patients diagnosed with squamous cell carcinomas were 183 (97.9%). The number of patients with FIGO stage IB1, IB2, IIA, IIB, IIIA, IIIB and IVA were 61 (32.6%), 7 (3.7%), 43 (23.0%), 62 (33.3%), 3 (1.6%), 7 (3.7%) and 4 (2.1%), respectively. External radiotherapy was performed with 6 MV or 10 MV X-rays, with a dose range of 19.8 Gy~ 50.4 Gy (median; 30.6), to whole pelvis. Intracavitary radiation (ICR) was then performed using a high-dose rate remote controlled afterloader with radioisotopes of Co-60 and Cs-137. The fraction size of the ICR was 5 Gy twice a week, and was delivered up to total doses of 10 Gy~ 55 Gy (median; 40). After the ICR, additional pelvic external radiotherapy with midline shielding width of 4 cm was performed with the dose range of 0~30.6 Gy (median; 19.8), and the resultant total doses of A points ranged between 49.8 Gy and 86.0 Gy (median; 70.6). RESULTS: The five-year overall survival rates of FIGO IB1, IB2, IIA, IIB, III and IVA were 88.3%, 83.3%, 86.1%, 65.2%, 60.0% and 50.0%, respectively (p=0.005). The pelvic control rates of each stage were 90.1%, 85.7%, 86.1%, 69.4%, 68.6% and 50.0%, respectively (p=0.03). From the multivariate analysis, the radiation response and tumor diameter were found to be significant factors affecting the overall survival. The significant factors influencing pelvic control were the radiation response and pre-treatment hemoglobin level. CONCLUSION: The radiation response and tumor diameter were significant factors affecting survival, so patients with tumor diameters greater than 4 cm should be considered for a combined modality, such as concurrent chemoradiotherapy.

Radiotherapy in Supraglottic Carcinoma: With Respect to Locoregional Control and Survival / 대한방사선종양학회지

PURPOSE: A retrospective study was undertaken to determine the role of conventional radiotherapy with or without surgery for treating a supraglottic carcinoma in terms of the local control and survival. MATERIALS AND METHODS: From Jan. 1986 to Oct. 1996, a total of 134 patients were treated for a supraglottic carcinoma by radiotherapy with or without surgery. Of them, 117 patients who had completed the radiotherapy formed the base of this study. The patients were redistributed according to the revised AJCC staging system (1997). The number of patients of stage I, II, III, IVA, IVB were 6 (5%), 16 (14%), 53 (45 %), 32 (27%), 10 (9%), respectively. Eighty patients were treated by radical radiotherapy in the range of 61.2~79.2 Gy (mean : 69.2 Gy) to the primary tumor and 45.0~93.6 Gy (mean : 54.0 Gy) to regional lymphatics. All patients with stage I and IVB were treated by radiotherapy alone. Thirty-seven patients underwent surgery plus postoperative radiotherapy in the range of 45.0~68.4 Gy (mean : 56.1 Gy) to the primary tumor bed and 45.0~59.4 Gy (mean : 47.2 Gy) to the regional lymphatics. Of them, 33 patients received a total laryngectomy (+-lymph node dissection), three had a supraglottic horizontal laryngectomy (+-lymph node dissection), and one had a primary excision alone. RESULTS: The 5-year survival rate (5YSR) of all patients was 43%. The 5YSRs of the patients with stage I+I, III+V were 49.9%, 41.2%, respectively (p=0.27). However, the disease-specific survival rate of the patients with stage I (n=6) was 100%. The 5YSRs of patients who underwent surgery plus radiotherapy (S+T) vs radiotherapy alone (RT) in stage II, III, IVA were 100% vs 43% (p=0.17), 62% vs 52% (p=0.32), 58% vs 6% (P<0.001), respectively. The 5-year actuarial locoregional control rate (5YLCR) of all the patients was 57%. The 5YLCR of the patients with stage I, II, III, IVA, IVB was 100%, 74%, 60%, 44%, 30%, respectively (p=0.008). The 5YLCR of the patients with S+T vs RT in stage II, III, IVA was 100% vs 68% (p=0.29), 67% vs 55% (p=0.23), 81% vs 20% (P<0.001), respectively. In the radiotherapy alone group, the 5YLCR of the patients with a complete, partial, and minimal response were 76%, 20%, 0%, respectively (P<0.001). In all patients, multivariate analysis showed that the N-stage, surgery or not, and age were significant factors affecting the survival rate and that the N-stage, surgery or not, and the ECOG performance index were significant factors affecting the locoregional control. In the radiotherapy alone group, multivariate analysis showed that the radiation response and N-stage were significant factors affecting the overall survival rate as well as locoregional control. CONCLUSION: In early stage supraglottic carcinoma, conventional radiotherapy alone is an equally effective modality compared to surgery plus radiotherapy and could preserve the laryngeal function. However, in the advanced stages, radiotherapy combined with concurrent chemotherapy for laryngeal preservation or surgery should be considered. In bulky neck disease, all the possible planned neck dissections after induction chemotherapy or before radiotherapy should be attempted.