A Novel Immunomodulatory Mechanism Dependent on Acetylcholine Secreted by Human Bone Marrow-derived Mesenchymal Stem Cells

BACKGROUND AND OBJECTIVES: Mesenchymal stem cells (MSCs) are used to treat autoimmune or inflammatory diseases. Our aim was to determine the immunomodulatory mechanisms elicited by MSCs during inflammation. METHODS AND RESULTS: We cocultured MSCs with peripheral blood mononuclear cells for a mixed lymphocyte reaction or stimulated them by phytohemagglutinin. Morphological changes of MSCs and secretion of acetylcholine (ACh) from MSCs were measured. The effects of an ACh antagonist and ACh agonist on lymphocyte proliferation and proinflammatory-cytokine production were determined. The inflammatory milieu created by immune-cell activation caused MSCs to adopt a neuronlike phenotype and induced them to release ACh. Additionally, nicotinic acetylcholine receptors (nAChRs) were upregulated in activated peripheral blood mononuclear cells. We observed that ACh bound to nAChR on activated immune cells and led to the inhibition of lymphocyte proliferation and of proinflammatory-cytokine production. MSC-mediated immunosuppression through ACh activity was reversed by an ACh antagonist called α-bungarotoxin, and lymphocyte proliferation was inhibited by an ACh agonist, ACh chloride. CONCLUSIONS: Our findings point to a novel immunomodulatory mechanism in which ACh secreted by MSCs under inflammatory conditions might modulate immune cells. This study may provide a novel method for the treatment of autoimmune diseases by means of MSCs.

Erratum: Mesenchymal Stem Cell Lines Isolated by Different Isolation Methods Show Variations in the Regulation of Graft-versus-host Disease

Typographical error has been detected in acknowledgements.

Mesenchymal Stem Cell Lines Isolated by Different Isolation Methods Show Variations in the Regulation of Graft-versus-host Disease

Since the discovery of the immunomodulation property of mesenchymal stem cells (MSCs) about a decade ago, it has been extensively investigated whether MSCs can be used for the treatment of immune-related diseases, such as graft-versus-host disease (GvHD). However, how to evaluate the efficacy of human MSCs for the clinical trial is still unclear. We used an MHC-mismatched model of GvHD (B6 into BALB/c). Surprisingly, the administration of the human MSCs (hMSCs) could reduce the GvHD-related mortality of the mouse recipients and xenogeneically inhibit mouse T-cell proliferation and IFN-gamma production in vitro. We recently established a new protocol for the isolation of a homogeneous population of MSCs called subfractionation culturing methods (SCM), and established a library of clonal MSC lines. Therefore, we also investigated whether MSCs isolated by the conventional gradient centrifugation method (GCM) and SCM show different efficacy in vivo. Intriguingly, clonal hMSCs (hcMSCs) isolated by SCM showed better efficacy than hMSCs isolated by GCM. Based on these results, the MHC-mismatched model of GvHD may be useful for evaluating the efficacy of human MSCs before the clinical trial. The results of this study suggest that different MSC lines may show different efficacy in vivo and in vitro.

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.

Nationwide Cancer Incidence in Korea, 2003-2005 / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To estimate the current cancer burden in Korea, newly diagnosed cancer cases and cancer incidence rates were calculated for the years 2003~2005. MATERIALS AND METHODS: The cancer incidence cases and rates were calculated from the Korea National Cancer Incidence Database. Crude and age-standardized incidence rates were calculated by gender for specified cancer sites in 5-year age groups. RESULTS: From 2003 to 2005, 398,824 cases of cancer were newly diagnosed in Korea (218,856 in men and 179,968 in women). For all sites combined, the crude incidence rate (CR) was 300.0 and 248.2 for men and women and the age-standardized incidence rate (ASR) was 297.0 and 191.2 per 100,000, respectively. Among men, five leading cancers were stomach (CR 66.0, ASR 64.2), lung (CR 48.5, ASR 50.3), liver (CR 44.9, ASR 42.1), colon and rectum (CR 37.9, ASR 37.2), and prostate cancer (CR 12.7, ASR 13.8). Among women, five leading cancers were breast (CR 37.3, ASR 29.0), thyroid (CR 36.2, ASR 28.8), stomach (CR 34.1, ASR 25.4), colon and rectum (CR 28.0, ASR 21.1), and lung cancer (CR 17.9, ASR 12.8). In the 0~14-year-old group, leukemia was the most common in both sexes; in the 15~34 group, the most common cancer was stomach cancer for men and thyroid cancer for women; in the 35~64 group, stomach cancer for men and breast cancer for women; among those 65 and over, lung cancer for men and stomach cancer, for women, respectively. CONCLUSION: The cancer incidence rates have increased in recent years, and more cancers are expected to develop as Korea is quickly becoming an aged society. The cancer incidence statistics in this report can be used as an important source to effectively plan and evaluate the cancer control program in Korea.

Postoperative Radiotherapy in the Rectal Cancers Patterns of Care Study for the Years of 1998~1999 / 대한방사선종양학회지

PURPOSE: To conduct a nationwide survey on the principles in radiotherapy for rectal cancer, and produce a database of Korean Patterns of Care Study. MATERIASL AND METHODS: We developed web-based Patterns of Care Study system and a national survey was conducted using random sampling based on power allocation methods. Eligible patients were who had postoperative radiotherapy for rectal cancer without gross residual tumor after surgical resection and without previous history of other cancer and radiotherapy to pelvis. Data of patients were inputted to the web based PCS system by each investigators in 19 institutions. RESULTS: Informations on 309 patients with rectal cancer who received radiotherapy between 1998 and 1999 were collected. Male to female ratio was 59 : 41, and the most common location of tumor was lower rectum (46%). Preoperative CEA was checked in 79% of cases and its value was higher than 6 ng/ml in 32%. Pathologic stage were I in 1.6%, II in 32%, III in 63%, and IV in 1.6%. Low anterior resection was the most common type of surgery and complete resection was performed in 95% of cases. Distal resection margin was less than 2 cm in 30%, and number of lymph node dissected was less than 12 in 31%. Chemotherapy was performed in 91% and most common regimen was 5-FU and leucovorine (69%). The most common type of field arrangement used for the initial pelvic field was the four field box (Posterior-Right-Left) technique (65.0%), and there was no AP-PA parallel opposing field used. Patient position was prone in 81.2%, and the boost field was used in 61.8%. To displace bowel outward, pressure modulating devices or bladder filling was used in 40.1%. Radiation dose was prescribed to isocenter in 45.3% and to isodose line in 123 cases (39.8%). Percent delivered dose over 90% was achieved in 92.9%. CONCLUSION: We could find the Patterns of Care for the radiotherapy in Korean rectal cancer patients was similar to that of US national survey. The type of surgery and the regimen of chemotherapy were variable according to institutions and the variations of radiation dose and field arrangement were within acceptable range.

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.

Survey on Radiotherpy Protocols for the Rectal Cancers among the Korean Radiation Oncologists in 2002 for the Development of the Patterns of Care Study of Radiation Therapy / 대한방사선종양학회지

PURPOSE: To conduct a nationwide survery on the principles in radiotherapy for rectal cancer, and develop the framework of a database of Korean Patterns of Care Study. MATERIALS AND METHODS: A consensus committee was established to develop a tool for measuring the patterns in radiotherapy protocols for rectal cancer. The panel was composed of radiation oncologists from 18 hospitals in Seoul Metropolitan area. The committee developed a survey format to analyze radiation oncologist's treatment principles for rectal cancer. The survey items developed for measuring the treatment principles were composed of 1) 8 eligibility criteria, 2) 20 items for staging work-ups and prognostic factors, 3) 7 items for principles of combined surgery and chemotherapy, 4) 9 patient set-ups, 5) 19 determining radiation fields, 6) 5 radiotherapy treatment plans, 7) 4 physical/laboratory examination to monitor a patient's condition during treatment, and 8) 10 follow-up evaluations. These items were sent to radiation oncologists in charge of gastrointestinal malignancies in all hospitals (48 hospitals) in Korea to which 30 replies were received (63%). RESULTS: Most of the survey items were replied to without no major differences between the repliers, but with the following items only 50% of repliers were in agreement:1) indications of preoperative radiation, 2) use of endorectal ultrasound, CT scan, and bone scan for staging work-ups, 3) principles of combining chemotherapy with radiotherapy, 4) use of contrast material for small bowel delineation during simulation, 5) determination of field margins, and 6) use of CEA and colonoscopy for follow-up evaluations. CONCLUSION: The items where considerable disagreement was shown among the radiation oncologists seemed to make no serious difference in the treatment outcome, but a practical and reasonable consensus should be reached by the committee, with logical processes of agreement. These items can be used for a basic database for the Patterns of Care Study, which will survey the practical radiotherapy patterns for rectal cancer in Korea.

Suggestion of Optimal Radiation Fields in Rectal Cancer Patients after Surgical Resection for the Development of the Patterns of Care Study / 대한방사선종양학회지

PURPOSE: To suggest the optimal radiation fields after a surgical resection based on a nationwide survey on the principles of radiotherapy for rectal cancer in the Korean Patterns of Care Study. MATERIALS AND METHODS: A consensus committee, composed of radiation oncologists from 18 hospitals in Seoul Metropolitan area, developed a survey format to analyze radiation oncologist's treatment principles for rectal cancer after a surgical resection. The survey format included 19 questions on the principles of defining field margins, and was sent to the radiation oncologists in charge of gastrointestinal malignancies in all Korean hospitals (48 hospitals). Thirty three (69%) oncologists replied. On the basis of the replies and literature review, the committee developed guidelines for the optimal radiation fields for rectal cancer. RESULTS: The following guidelines were developed: superior border between the lower tip of the L5 vertebral body and upper sacroiliac joint; inferior border 2~3 cm distal to the anastomosis in patient whose sphincter was saved, and 2~3 cm distal to the perineal scar in patients whose anal sphincter was sacrificed; anterior margin at the posterior tip of the symphysis pubis or 2~3 cm anterior to the vertebral body, to include the internal iliac lymph node and posterior margin 1.5~2 cm posterior to the anterior surface of the sacrum, to include the presacral space with enough margin. Comparison with the guidelines, the replies on the superior margin coincided in 23 cases (70%), the inferior margin after sphincter saving surgery in 13 (39%), the inferior margin after abdominoperineal resection in 32 (97%), the lateral margin in 32 (97%), the posterior margins in 32 (97%) and the anterior margin in 16 (45%). CONCLUSION: These recommendations should be tailored to each patient according to the clinical characteristics such as tumor location, pathological and operative findings, for the optimal treatment. The adequacy of these guidelines should be proved by following the Korean Patterns of Care Study.

Correction Method on Mismatched Posterior Edge of Medial and Lateral Tangential Fields for Three Fields Techniques in Breast Cancer / 대한방사선종양학회지

PURPOSE: The target volume for the three field technique in breast cancer include the breast tangential and supraclavicular areas. The techniques rotating the gantry and couch angles, to match these two areas, will geometrically produce mismatching of the posterior edge between the medial and lateral tangential beams. This mismatch was confirmed by film dosimetry and three-dimensional computer planning. The correction methods of this mismatching were studied in this article. MATERIALS AND METHODS: After the supraclavicular field was simulated using a half beam block and the medial and lateral tangential fields, by the rotation of the couch and gantry, we compared the following two methods to correct the mismatch. The first method was the rotation of collimator until a line drawn on the posterior edge of tangential beams before the rotation of couch aligned the line drawn on the posterior edge after the rotation. The second method was the rotation of collimator according to the formula developed by the author as follows; Co=2sin(-1){sin angle x sin (C/2)} (Co: collimator angle, angle: angle between tangential beam and table, C: couch angle) RESULTS: The film dosimetry showed the mismatching of posterior edges of the medial and lateral tangential fields prior to the rotation of collimator, while the posterior edges matched well after the rotation of collimator according to the formula. The three-dimensional computer plan also showed that the posterior edges matched well after the rotation of collimator accordingly. The DVH of the ipsilateral lung with the proper rotation of collimator angle was better than that without the rotation of collimator angle. CONCLUSION: The mismatching of the posterior edges of the medial and lateral tangential fields can be recognized on the three field technique in breast irradiation when the gantry and couch are simultaneously rotated and can be corrected with the proper rotation of the collimator angle. The radiation dose to the ipsilateral lung could be lowered with this technique.

Intraluminal Brachytherapy after Metallic Stent Placement in Primary Bile Duct Carcinoma

PURPOSE: To determine the effect of intraluminal brachytherapy on stent patency and survival after metallic stent placement in patients with primary bile duct carcinoma. MATERIALS AND METHODS: Twenty-seven patients with primary bile duct carcinoma underwent metallic stent placement; in 16 of the 27 intraluminal brachytherapy with an iridium-192 source (dose, 25 Gy) was the performed. Obstruction was due to either hilar (n=14) or non-hilar involvement (n=13). For statistical comparison of patients who underwent/did not undergo intraluminal brachytherapy, stent patency and survival were calculated using the Kaplan-Meier method and an independent t test. RESULTS: The mean durations of stent patency and survival were 9.1 and 10.0 months respectively in patients who underwent intraluminal brachytherapy, and 4.2 and 5.0 months in those who did not undergo this procedure (p<0.05). The mean durations of stent patency and survival among the 22 patients who died were 7.6 (range, 0.8 -16.1) and 8.3 (range, 0.8-17.3) months, respectively, in the eleven patients who underwent intraluminal brachytherapy, and 4.2 (range, 0.9-8.0) and 5.0 (range, 0.9-8.4) months in those whom the procedure was not performed (p<0.05). CONCLUSION: Intraluminal brachytherapy after stent placement extended both stent patency and survival in patients with primary bile duct carcinoma.

Evaluation of Staging with MR Imaging in the Uterine Cervical Cancer / 대한암학회지

PURPOSE: Uterine cervical carcinoma is the most common cancer in Korean women. We evaluated the accuracy of magnetic resonance (MR) imaging in determining the stage and extent of disease in cervical carcinoma. MATERIALS AND METHODS: From January 1994 through December 1996, in all 35 patients, MR imaging was performed before any operative procedure. With a 1.5T superconducting magnet, TR (repetition time)/TE (echo time) of 483/9msec for T1-weighted images and 3750/98msec for T2-weighted images were used. All patients underwent radical hysterectomy or total abdominal hysterectomy and had detailed histologic evaluation. MR image were reviewed and compared with pathologic findings on the presence of tumor size, depth of stromal invasion and vagina extension. RESULTS: The accuracy of MRI in determination of stage was 74%. Its accuracy was 60% for the assessment of tumor size. Tumor size was underestimated in 6 patients (17%) and overestimated in 8 patients (23%). Tumor infiltration into the stroma was classified as no, partial, complete. The accuracy of MRI in cervical stromal invasion was 66%. CONCLUSION: MR is a relatively promising method for staging and evaluating extent of disease in carcinoma of the uterine cervix.

Objective Analysis of the Set-up Error and Tumor Movementin Lung Cancer Patients using Electronic Portal Imaging Device / 대한치료방사선과학회지

PURPOSE: The aim of this study is to investigate the random and systematic errors and tumor movement using electronic portal imaging device in lung cancer patients for the adequate margin in the treatment planning of 3-dimensional conformal therapy. METHODS AND MATERIALS: The electronic portal imaging device is matrix ion chamber type(Portal Vision, Varian). Ten patients of lung cancer treated with chest irradiation were selected for this study. Patients were treated in the supine position without immobilization device. All treatments were delivered by an 10 MV linear accelerator that had the portal imaging system mounted to its gantry. AP or PA field portal images were only analyzed. Radiation therapy field included the tumor, mediastinum, and supraclavicular lymph nodes. A total of 103 portal images wereanalyzed for set-up deviation and 10 multiple images were analyzed for tumor movement because of respiration and cardiac motion. RESULTS: The average values of setup displacements in the x, y direction was 1.41 mm, 1.78 mm, respectively. The standard deviation of systematic component was 4.63 mm, 4.11mm along the x,y axis, respectively while the random component was 4.17 mm in the x direction and 3.31 mm in the y direction. The average displacement from respiratory movement was 12.2 mm with a standard deviation of 4.03 mm CONCLUSION: The overall set-up displacement includes both random and systematic component and respiratory movement. About 10 mm, 25 mm margins along x,y axis which considered the set-up displacement and tumor movement were required for initial 3-dimensional conformal treatment planning in the lung cancer patients and portal images should be madeand analyzed during first week of treatment, individually.

Optimum Dose Combination of External Radiation and High Dose Rate ICR in FIGO IB Uterine Cervical Cancer / 대한치료방사선과학회지

PURPOSE: To assess the efficacy of high dose rate - intracavitary radiotherapy (HDR-ICR) in the radiotherapy of FIGO stage IB squamous cell carcinoma of uterine cervix and to determine the optimum dose combination xheme of external radiotherapy and ICR to achieve acceptable local control without severe complication. METHODS AND MATERIALS: One hundred and sixty two patients with FIGO stage Ib squamous cell carcinoma of uterine cervix who received definitive radiotherapy between May 1979 and December 1990 were retrospectively analyzed. All the patients received external radiotherapy combined with HDR-ICR. External dose of 40-46 Gy in 4.5-5 weeks was given to whole pelvis(median 45 Gy) and ICR dose of 30-39 Gy in 10-13 times was given to the point A. Midline shielding was done after 20-45 Gy of external radiotherapy(median 40 Gy). Summation of external dose plus ICR dose to the point A range were 64.20-95.00 Gy, and mean was 83.94 Gy. We analyzed the local control rate, survival rate, and late complication rate. RESULTS: Initial complete response rate was 99.4% for all patients. Overall 5-year survival rate was 91.1% and 5-year disease free survival rate was 90.9%. Local failure rate was 4.9% and distant failure rate was 4.3% Tumor size was the only significant prognostic factor. When tumor size greater than 3cm, 5-year survival rate was 92.6% and less than 3cm, that was 79.6%, Late complication rate was 23.5% with 18.5% of rectal complication and 4.9% of bladder complication. Mean rectal dose summation of external midline dose plus ICR rectal point dose was lower in the patients without rectal complication(74.88 Gy) than those with rectal complication (78.87 Gy). Complication rate was inceased with low rate of improvement of survival rate when summation of external midline dose plus point A or point R dose by ICR was greater than 70-75 Gy. CONCLUSION: The definitive radiation therapy using high dose rate ICR in FIGO stage IB uterine cervical cancer is effective treatment modality with good local control and survival rate without severe complication.

Late Rectal Complication in Patients Treated with High Dose Rate Brachytherapy for Stage IIB Carcinoma of the Cervix / 대한치료방사선과학회지

PURPOSE: This paper reports a dosimetric study of 88 patients treated with a combination of external radiotherapy and high dose rate ICR for FIGO stage IIB carcinoma of the cervix. The purpose is to investigate the correlation between the radiation doses to the rectum. external radiation dose to the whole pelvis. ICR reference volume. TDF, BED and the incidence of late rectal complications, retrospectively METHODS AND MATERIALS: From November 1989 through December 1992, 88 patients with stage IIB cervical carcinoma received radical radiotherapy at Department or Radiation Oncology in Yonsei University Hospital. Radiotherapy consisted of 44-54 Gy(median 49 Gy) external beam irradiation plus high dose rate intracavitary brachy therapy with 5 Gy per fraction twice a week to a total dose of 30 Gy on point A. The maximum dose to the rectum by contrast(r,R) and reference rectal dose by ICRU 38(dr, DR) were calculated. The ICR reference volume was calculated by Gamma Dot 3.11 HDR planning system, retrospectively. The time-dose factor(TDF) and the biologically effective dose (BED) were calculated. RESULTS: Twenty seven(30.7%) of the 88 patients developed late rectal complications : 12 patients(13.6%) for grade 1, 12 patients(13.6%) for grade 2 and 3 patients(3.4%) for grade 3. We found a significant correlation between the external whole pelvis irradiation dose and grade 2, 3 rectal complicaition. The mean dose to the whole pelvis for the group of patients with grade 2, 3 complication was higher, 4093.3+/-453.1 cGy, than that for the patients without complication 3873.8+/-415.6 (0.05p<0.1). The gradual increase in the frequency of grade 2, 3 rectal compication increased as a function of the dose of external beam therapyto the whole pelvis(midline shielding start dose) and total rectal dose. The mean total rectal dose by rectal barium(R) for the group of patients with grade 2, 3 rectal complication was higher, 7163.0+/-838.5 cGy, than that for the patients without rectal complication, 6772.7+/-884.0(p<0.05). There was no correlation of the rate of grade 2, 3 rectal complication with the ICR rectal doses(r,dr), ICR reference volume, TDF and BED. CONCLUSION: This investigation has revealed a significant correlation between the dose calculated at the rectal dose by ICRU 38(DR) or the most anterior rectal dose by contrast(R), dose to the whole pelvis and the incidence of grade 2,3 late rectal complications in patients with stage IIB cervical cancer undergoing external beam radiotherapy and HDR ICR. Thus there rectal reference points doses and whole pelvis dose appear to be useful prognostic indicators of late rectal complication in high dose rate ICR treatment in cervical carcinoma.

Analysis of Prognostic Factors in Glioblastoma Multiforme / 대한치료방사선과학회지

PURPOSE: To find the more effective treatment methods that improving thesurvival of patients with glioblastoma multiforme(GBM), we analyze the prognostic factors and the outcome of therapy in patients with GBM. METHODS AND MATERIALS: One hundred twenty-one patients with a diagnosis of GBM treated at Severance Hospital between 1973 and 1993 were analyzed for survival with respect to patients characteristics, that is, duration of symptom, age, and Karnofsky performance status, as well as treatment related variables such as extent of surgery and radiotherapy. RESULTS: The median survival time(MST) and 2-year overall survival rate (OSR) of the patients with GBM were 13 months and 20.8%, respectively. Duration of symptom, age, Karnofsky performance status(KPS), radiotherapy, and extent of surgical resection were associated with improved survival in a univariate analysis. Patients whose duration of symptom was longer than 3 months, had the 2-year OSR of 47.2%(p=0.0082), who were younger than age 50, 32.9%(p=0.0003). In patients with a KPS of 80 or higher, the 2 year OSR was 36.9%(p=0.0422). Patients undergoing radiotherapy had the 2-year OSR of 22.9%(p=0.030), and surgical resection of 23.3%(p<0.000). A cox regression model confirmed a significant correlation of duration of symptom, age, radiotherapy,and extent of surgical resection with survival, excluding KPS(p=0.8823). The 2-year OSR were 22.3% and 19.4%, combined with chemotherapy or without, respectively(p=0.06028). The duration of symptom of 3 months or shorter. 50 years of age or older, and undergoing stereotactic biopsy only were considered as risk factors. then patients without any risk factors had the MST of 29 months and 2-year OSR of 53.9% compared to 4 months and 0% for patients who had all 3 risk factors. Most of all treatment failure occurred in the primary tumor site(86.4%) CONCLUSION: The duration of symptom, age, radiotherapy, and extent of surgical resection were a prognostically significant independent variables. To get a better survival, it seems to be reasonable that the study design which improves the local control rates is warranted.

The Role of Intraluminal Brachytherapy in Management of Esophageal Cancer / 대한치료방사선과학회지

PURPOSE: To evaluate our clinical experience with the combination of teletherapy and intraluminal brachytherapy in patients with unresectable or inoperable esophageal cancers. MATERIALS AND METHODS: From Nov. 1989 to Mar. 1993, twenty patients with esophageal cancer were treated with radical radiotherapy and intraluminal brachytherapy at Yonsei Cancer Center. All patients had squamous histology and stage distribution was as follows: stage II, 4(20%) patients; III, 15(75%) patients; IV, 1(5%) patients. A dose of 5-12 Gy/1-3 weeks with intraluminal brachytherapy (3-5 Gy/fraction) to 5mm from the outside of the esophageal tube using high dose rate iridium-192 reotely afterloading bracytherapy machine was given 2 weeks after a total dose of 59-64Gy with external radiotherapy. Induction chemotherapy using cisplatin and 5-FU was performed in 13 patients with median 3 cycles(1-6 cycles). Response rate, local control rate, survival and complications were analysed retrospectively. RESULTS: Two-year overall survival rate and median survival were 15.8% and 13.5 months. Resonse rates were as follows: complete remission(CR) 5(25%); partial remission a(Pra) 7(35%); partial remission b(PRb) 7(35%); no response(NR) 1(5%). Patterns of failure were as follows : local failure 13(65%), local and distant failure 3(15%), distant failure 0(0%). Ultimate local control rate was 20%. Treatment related complications included esophageal ulcer in two patients and esophageal stricture in one. CONCLUSION: Though poor local control rate, median survival was improved as compared with previous results of radiation therapy alone(8months) and chemo-radiation combined treatment(11months) in Yonsei Cancer Center. High-dose-rate intraluminal brachytherapy following external irradiation is an effective treatment modality with acceptable toxicity in esophageal cancer.

Comparative Analysis between preoperative Radiatherapy and postoperative Radiotherapy in Clinical Stage I and II Endometrial Carcinoma / 대한치료방사선과학회지

PURPOSE: To obtain the optical treatment method in patients with endometrial carcinoma(clinical stage FIGO I, II) by comparative analysis between preoperative radiotherapy(pre-op R) and postoperative radiotherapy(post-op RT). MATERIALS AND METHODS: A retrospctive review of 62 endometrial carcinoma patients referred to the Yonsei Cancer Center for radiotherapy between 1985 and 1991 was undertaken. Of 62 patients, 19 patients(Stage I; 12 patients, Stage II; 7 patients) received pre-op RT before TAH(Total Abdominal Hysterectomy) and BSO(Bilateral Salphingoophorectomy) (Group 1) and 43 patients( Stage 1; 32 patients, Stage 2; 11 patients) received post-op RT after TAH and BSO (Group 2). Pre-op irradiation was given 4-6 weeks prior to surgery and post-op RT was administered on 4-5 weeks following surgery. All patients exept 1 patient(Group2; ICR alone) received external irradiation. Seventy percent(13/19) of pre-op RT group and 54 percent(23/42) of post-op RT group received external pelvic irradiation and intracavitary radiation therapy(ICR). External radiation dose was 39.6-55Gy(median 45Gy) in 5-6week through opposed AP/PA fields or 4-field box technique treating daily, five days per week, 180cGy per fraction. ICR doses were prescreibed to point A(20-39.6 Gy, median 39Gy) in Group 1 and 0.5cm depth from vaginal surface (18-30 Gy, median 21Gy) in Group2. RESULTS: The overall 5year survival rate was 95%. No survival difference between pre-op and post-op RT group.(89.3% vs 97.7%, p>0.1) There was no survival difference by stage, grade and histology between two groups. The survival rate was not affected by presence of residual tumor of surgical specimen after pre-op RT in Group 1(p>0.1), but affected by presence of lymph node metastasis in post-op RT group(p<0.5). The complication rate of pre-op RT group was higher than post-op RT.(16% vs 5%) CONCLUSION: Post-op radiotherapy offers the advantages of accurate surgical-pathological staging and low complication rate.

Dosimetric Characteristics on Penumbra Regions of the multileaf Collimator as Compared with the Lead Alloy Block / 대한치료방사선과학회지

PURPOSE: The Conformal Radiation Therapy has been widely used under favour of development of computer technologies. The delivery of a large number of static radiation fields are being necessary for the conformal irradiation. In this paper, we investigate dosimetric characteristics on penumbra regions of a multileaf collimator(MLC), and compare to those of lead alloy block for he optimal use of the system in 3-D conformal radiotherapy. MATERIALS AND METHODS: The measurement of penumbra by MLC or lead alloy block was performed with 6 or 10 MV X-rays. The film was positioned at a dmax depth and 10 cm depth, and its optical density was determined using a scanning videodensitometer. The effective penumbra, the distance from 80% to 20% isodose lines and 90 to 10 were analyzed as a function of the angle between the direction of leaf motion and the edge defined by leaves. RESULTS: Increasing MLC angle (0-75degree) was observed with increasing the penumbra widths and the scalloping effect. There was no definite differences of penumbra width from 80% to 20% isodose lines, while being the small increase of penumbra width of lead alloy block are agree reasonably with those of MLC within 4.8mm. CONCLUSION: The comparative qualitative study of the penumbra between MLC and lead alloy block demonstrate the clinical acceptability and suitability of the multileaf collimator for 3-D conformal radiotherapy.

Dosimetric Characteristics on Penumbra Regions of the multileaf Collimator as Compared with the Lead Alloy Block / 대한치료방사선과학회지

PURPOSE: The Conformal Radiation Therapy has been widely used under favour of development of computer technologies. The delivery of a large number of static radiation fields are being necessary for the conformal irradiation. In this paper, we investigate dosimetric characteristics on penumbra regions of a multileaf collimator(MLC), and compare to those of lead alloy block for he optimal use of the system in 3-D conformal radiotherapy. MATERIALS AND METHODS: The measurement of penumbra by MLC or lead alloy block was performed with 6 or 10 MV X-rays. The film was positioned at a dmax depth and 10 cm depth, and its optical density was determined using a scanning videodensitometer. The effective penumbra, the distance from 80% to 20% isodose lines and 90 to 10 were analyzed as a function of the angle between the direction of leaf motion and the edge defined by leaves. RESULTS: Increasing MLC angle (0-75degree) was observed with increasing the penumbra widths and the scalloping effect. There was no definite differences of penumbra width from 80% to 20% isodose lines, while being the small increase of penumbra width of lead alloy block are agree reasonably with those of MLC within 4.8mm. CONCLUSION: The comparative qualitative study of the penumbra between MLC and lead alloy block demonstrate the clinical acceptability and suitability of the multileaf collimator for 3-D conformal radiotherapy.