Clinical Significance of FDG PET-CT Scan at 12 Weeks after Curative Radiation Therapy in Patients with Head and Neck Cancer / 대한두경부종양학회지

Background/Objectives@#To evaluate clinical significance of FDG PET-CT for detection of residual cancer cells after curative radiation therapy or chemoradiotherapy for patients with squamous cell carcinoma (SCC) of Head and NeckMaterials & Methods: A retrospective analysis of patients with SCC of Head and neck with curative radiotherapy or chemoradiotherpy between June 2011 and Jan. 2019 was performed. Sixty patients were treated with Intensity-modulated radiotherapy (IMRT). The Metabolic responses were evaluated on the post-treatment FDG PET-CT at 12 weeks after curative radiotherapy completion. @*Results@#Median follow up was 51.5 months (3-102). The overall survival (OS), disease free survival (DFS), local control rate (LCR), and Distant metastasis free survival (DMFS) at 5 years were 80.5%, 80.1%, 87.7% and 89.1%. Metabolic CR was found in 43 (71.7%) and partial metabolic response (PR) was noted in 17 (14.6%). Metabolic CR was significantly correlated with OS, DFS, LCR, and DMFS. On multivariate analysis, Metabolic CR remained significant for DFS and LCR. @*Conclusion@#Metabolic CR on post-radiotherapy FDG PET-CT is highly predictive of increased DFS and LCR in patients with head and neck cancer.

Clinical Significance of FDG PET-CT Scan at 12 Weeks after Curative Radiation Therapy in Patients with Head and Neck Cancer / 대한두경부종양학회지

Background/Objectives@#To evaluate clinical significance of FDG PET-CT for detection of residual cancer cells after curative radiation therapy or chemoradiotherapy for patients with squamous cell carcinoma (SCC) of Head and NeckMaterials & Methods: A retrospective analysis of patients with SCC of Head and neck with curative radiotherapy or chemoradiotherpy between June 2011 and Jan. 2019 was performed. Sixty patients were treated with Intensity-modulated radiotherapy (IMRT). The Metabolic responses were evaluated on the post-treatment FDG PET-CT at 12 weeks after curative radiotherapy completion. @*Results@#Median follow up was 51.5 months (3-102). The overall survival (OS), disease free survival (DFS), local control rate (LCR), and Distant metastasis free survival (DMFS) at 5 years were 80.5%, 80.1%, 87.7% and 89.1%. Metabolic CR was found in 43 (71.7%) and partial metabolic response (PR) was noted in 17 (14.6%). Metabolic CR was significantly correlated with OS, DFS, LCR, and DMFS. On multivariate analysis, Metabolic CR remained significant for DFS and LCR. @*Conclusion@#Metabolic CR on post-radiotherapy FDG PET-CT is highly predictive of increased DFS and LCR in patients with head and neck cancer.

The Effect of Hospital Case Volume on Clinical Outcomes in Patients with Nasopharyngeal Carcinoma: A Multi-institutional Retrospective Analysis (KROG-1106) / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to investigate the effect of hospital case volume on clinical outcomes in patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Data on 1,073 patients with cT1-4N0-3M0 NPC were collected from a multi-institutional retrospective database (KROG 11-06). All patients received definitive radiotherapy (RT) either with three-dimensional-conformal RT (3D-CRT) (n=576) or intensity-modulated RT (IMRT) (n=497). The patients were divided into two groups treated at high volume institution (HVI) (n=750) and low volume institution (LVI) (n=323), defined as patient volume ≥ 10 (median, 13; range, 10 to 18) and < 10 patients per year (median, 3; range, 2 to 6), respectively. Endpoints were overall survival (OS) and loco-regional progression-free survival (LRPFS). RESULTS: At a median follow-up of 56.7 months, the outcomes were significantly better in those treated at HVI than at LVI. For the 614 patients of propensity score-matched cohort, 5-year OS and LRPFS were consistently higher in the HVI group than in the LVI group (OS: 78.4% vs. 62.7%, p < 0.001; LRPFS: 86.2% vs. 65.8%, p < 0.001, respectively). According to RT modality, significant difference in 5-year OS was observed in patients receiving 3D-CRT (78.7% for HVI vs. 58.9% for LVI, p < 0.001) and not in those receiving IMRT (77.3% for HVI vs. 75.5% for LVI, p=0.170). CONCLUSION: A significant relationship was observed between HVI and LVI for the clinical outcomes of patients with NPC. However, the difference in outcome becomes insignificant in the IMRT era, probably due to the standardization of practice by education.

Survey of the Patterns of Using Stereotactic Ablative Radiotherapy for Early-Stage Non-small Cell Lung Cancer in Korea / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Stereotactic ablative radiotherapy (SABR) is an effective emerging technique for early-stage non-small cell lung cancer (NSCLC). We investigated the current practice of SABR for early-stage NSCLC in Korea. MATERIALS AND METHODS: We conducted a nationwide survey of SABR for NSCLC by sending e-mails to all board-certified members of the Korean Society for Radiation Oncology. The survey included 23 questions focusing on the technical aspects of SABR and 18 questions seeking the participants' opinions on specific clinical scenarios in the use of SABR for early-stage NSCLC. Overall, 79 radiation oncologists at 61/85 specialist hospitals in Korea (71.8%) responded to the survey. RESULTS: SABR was used at 33 institutions (54%) to treat NSCLC. Regarding technical aspects, the most common planning methods were the rotational intensity-modulated technique (59%) and the static intensity-modulated technique (49%). Respiratory motion was managed by gating (54%) or abdominal compression (51%), and 86% of the planning scans were obtained using 4-dimensional computed tomography. In the clinical scenarios, the most commonly chosen fractionation schedule for peripherally located T1 NSCLC was 60 Gy in four fractions. For centrally located tumors and T2 NSCLC, the oncologists tended to avoid SABR for radiotherapy, and extended the fractionation schedule. CONCLUSION: The results of our survey indicated that SABR is increasingly being used to treat NSCLC in Korea. However, there were wide variations in the technical protocols and fractionation schedules of SABR for early-stage NSCLC among institutions. Standardization of SABR is necessary before implementing nationwide, multicenter, randomized studies.

The Role of Neoadjuvant Chemotherapy in the Treatment of Nasopharyngeal Carcinoma: A Multi-institutional Retrospective Study (KROG 11-06) Using Propensity Score Matching Analysis / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We compared the treatment results and toxicity in nasopharyngeal carcinoma (NPC) patients treated with concurrent chemotherapy (CCRT) alone (the CRT arm) or neoadjuvant chemotherapy followed by CCRT (the NCT arm). MATERIALS AND METHODS: A multi-institutional retrospective study was conducted to review NPC patterns of care and treatment outcome. Data of 568 NPC patients treated by CCRT alone or by neoadjuvant chemotherapy followed by CCRT were collected from 15 institutions. Patients in both treatment arms were matched using the propensity score matching method, and the clinical outcomes were analyzed. RESULTS: After matching, 300 patients (150 patients in each group) were selected for analysis. Higher 5-year locoregional failure-free survival was observed in the CRT arm (85% vs. 72%, p=0.014). No significant differences in distant failure-free survival (DFFS), disease-free survival (DFS), and overall survival were observed between groups. In subgroup analysis, the NCT arm showed superior DFFS and DFS in stage IV patients younger than 60 years. No significant difference in compliance and toxicity was observed between groups, except the radiation therapy duration was slightly shorter in the CRT arm (50.0 days vs. 53.9 days, p=0.018). CONCLUSION: This study did not show the superiority of NCT followed by CCRT over CCRT alone. Because NCT could increase the risk of locoregional recurrences, it can only be considered in selected young patients with advanced stage IV disease. The role of NCT remains to be defined and should not be viewed as the standard of care.

Patterns of care for patients with nasopharyngeal carcinoma (KROG 11-06) in South Korea

PURPOSE: To investigate the patterns of care for patients with nasopharyngeal carcinoma (NPC) in South Korea. MATERIALS AND METHODS: A multi-institutional retrospective study was performed (Korean Radiation Oncology Group [KROG] 11-06) on a total of 1,445 patients from 15 institutions. RESULTS: Of the 1,445 patients, more than half were stages III (39.9%) and IV (35.8%). In addition to patterns of care, we also investigated trends over time with the periods 1988-1993, 1994-2002, and 2003-2011. The frequencies of magnetic resonance imaging and positron emission tomography-computed tomography were markedly increased in the third period compared to previous 2 periods. Concurrent chemoradiation (CCRT) was performed on 894 patients (61.9%), neoadjuvant chemotherapy on 468 patients (32.4%), and adjuvant chemotherapy on 366 patients (25.3%). Of stage II-IV patients, CCRT performed on 78.8% in 2003-2011 compared to 15.0% in 1988-1993. For patients treated with CCRT, cisplatin was the most commonly used agent in 81.3% of patients. Over the periods of time, commonly used radiotherapy (RT) techniques were changed from 2-dimensional RT (1988-1993, 92.5%) to 3-dimensional RT (2003-2011, 35.5%) or intensity-modulated RT (IMRT; 2003-2011, 56.5%). Median RT doses given to primary tumors, high-risk lymphatics, and low-risk lymphatics were 70.0 Gy, 58.1 Gy, and 48.0 Gy, respectively. Adoption of IMRT increased the dose per fraction and escalated total radiation dose. CONCLUSION: Assessment of the patterns of care for NPC patients in South Korea demonstrated that management for NPC including diagnostic imaging, treatment regimen, RT techniques and dose schedule, advanced in accordance with the international guidelines.

Retrospective analysis of treatment outcomes after postoperative chemoradiotherapy in advanced gastric cancer

PURPOSE: To evaluate retrospectively the survival outcome, patterns of failure, and complications in patients treated with postoperative chemoradiotherapy (CRT) in advanced gastric cancer. MATERIALS AND METHODS: Between January 2000 and December 2006, 80 patients with advanced gastric cancer who received postoperative concurrent CRT were included. Pathological staging was IB-II in 9%, IIIA in 38%, IIIB in 33%, and IV in 21%. Radiotherapy consisted of 45 Gy of radiation. Concurrent chemotherapy consisted of a continuous intravenous infusion of 5-fluorouracil and leucovorin on the first 4 days and last 3 days of radiotherapy. RESULTS: The median follow-up period was 48 months (range, 3 to 83 months). The 5-year overall survival, disease-free survival, and locoregional recurrence-free survivals were 62%, 59%, and 80%, respectively. In the multivariate analysis, significant factors for disease-free survival were T stage (hazard ratio [HR], 0.278; p = 0.038), lymph node dissection extent (HR, 0.201; p = 0.002), and maintenance oral chemotherapy (HR, 2.964; p = 0.004). Locoregional recurrence and distant metastasis occurred in 5 (6%) and 18 (23%) patients, respectively. Mixed failure occurred in 10 (16%) patients. Grade 3 leukopenia and thrombocytopenia were observed in 4 (5%) and one (1%) patient, respectively. Grade 3 nausea and vomiting developed in 8 (10%) patients. Intestinal obstruction developed in one (1%). CONCLUSION: The survival outcome of the postoperative CRT in advanced gastric cancer was similar to those reported previously. Our postoperative CRT regimen seems to be a safe and effective method, reducing locoregional failure without severe treatment toxicity in advanced gastric cancer patients.

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.

Accuracy Evaluation of Treatment Planning System Using Irregular-surface Water Phantom / 의학물리

We evaluated on the calculation accuracy of treatment planning system (TPS) with phantom having convex and concave surface. The TPS is Eclipse (Varian, USA) using both algorithms AAA and PBC for photon dose calculations. PBC algorithms have three corrections of Batho, modified Batho (M-Batho), and equivalent TAR (E-TAR). The field sizes were 10x10 cm2 and 20x20 cm2, and MLC-shaped fields for these fields. We measured doses at three depths 5, 10 and 15 cm in phantom of SSD=90 cm in the condition of inserted farmer chamber. For given conditions, we have calculated dose with these algorithms and compared them with measured doses. In AAA the calculated doses (dose/MU) were agreed to measured doses within +/-1% in flat and convex surface and were under estimated with -1.9% maximum in concave surface. In PBC the calculated doses were over estimated with +1.7% and +4.1% respectively in flat and convex surface and the differences were from -3.1% to +2.1% in concave surface. In comparison of criteria from AAPM and IAEA reports, and statistical analysis for these results, it is found that the AAA's results are in good agreement with measured values and the M-Batho's results are generally good agreed with measured values among PBC algorithms.

The Clinical Significance of Cathepsin D and p53 Expressionin Locally Advanced Rectal Cancer / 대한방사선종양학회지

PURPOSE: Cathepsin D (CD) is a lysosomal acid proteinase that is related to malignant progression, invasion, and a poor prognosis in several tumors. The aim of this study was to evaluate the prognostic clinical significance of CD and p53 expression in pretreatment biopsy specimens from patients with locally advanced rectal cancer who were treated with preoperative chemoradiation. MATERIALS AND METHODS: Eighty-nine patients with locally advanced rectal cancer (cT3/T4 or N+) were included in this study. Preoperative chemoradiation consisted of a dose of 50.4 Gy of pelvic radiation and two concurrent cycles of administration of 5-fluorouracil and leucovorin. Surgery was performed six weeks after chemoradiation. CD and p53 expression in pretreatment formalin-fixed paraffin-embedded tumor biopsy specimens were assessed by immunohistochemical staining using a CD and p53 monoclonal antibodies. The threshold value for a positive stain in tumor tissue and stromal cells was 1+ intensity in 10% of the tumors or stromal cells, respectively. RESULTS: Positive CD expression was found in 57 (64%) of the tumors and 32 (35%) of the stromal cell specimens. There was no association with CD expression of the tumor or stromal cells and patient characteristics. There was a correlation between tumor CD expression with stromal cell CD expression (p=0.01). Overexpression of p53 was not a significant prognostic factor. The 5-year overall survival (OS) and disease-free survival (DFS) rates were not different between tumor CD-negative and positive patient biopsy samples (69% vs. 65%, 60% vs. 61%, respectively). The 5-year OS rates in the tumor-negative/stromal cell-negative, tumor-negative/stromal cell-positive, tumor-positive/stromal cell-negative and tumor-positive/ stromal cell-positive biopsy samples were 75%, 28%, 62%, and 73%, respectively. Stromal cell staining only without positive tumor staining demonstrated the worst overall survival prognosis for patients (p=0.013). CONCLUSION: Overexpression of p53 in rectal biopy tissue was not associated with prognostic significance. In the pretreatment biopsy specimens, an exclusive increase in CD expression in stromal cells without tumor expression was related to poor overall survival in patients with locally advanced rectal cancer treated with preoperative chemoradiation.

The 1998, 1999 Patterns of Care Study for Breast Irradiation after Mastectomy in Korea / 대한방사선종양학회지

PURPOSE: To determine the patterns of evaluation and treatment in patients with breast cancer after mastectomy and treated with radiotherapy. A nationwide study was performed with the goal of improving radiotherapy treatment. MATERIALS AND METHODS: A web-based database system for the Korean Patterns of Care Study (PCS) for 6 common cancers was developed. Randomly selected records of 286 eligible patients treated between 1998 and 1999 from 17 hospitals were reviewed. RESULTS: The ages of the study patients ranged from 20 to 80 years (median age 44 years). The pathologic T stage by the AJCC was T1 in 9.7% of the cases, T2 in 59.2% of the cases, T3 in 25.6% of the cases, and T4 in 5.3% of the cases. For analysis of nodal involvement, N0 was 7.3%, N1 was 14%, N2 was 38.8%, and N3 was 38.5% of the cases. The AJCC stage was stage I in 0.7% of the cases, stage IIa in 3.8% of the cases, stage IIb in 9.8% of the cases, stage IIIa in 43% of the cases, stage IIIb in 2.8% of the cases, and IIIc in 38.5% of the cases. There were various sequences of chemotherapy and radiotherapy after mastectomy. Mastectomy and chemotherapy followed by radiotherapy was the most commonly performed sequence in 47% of the cases. Mastectomy, chemotherapy, and radiotherapy followed by additional chemotherapy was performed in 35% of the cases, and neoadjuvant chemoradiotherapy was performed in 12.5% of the cases. The radiotherapy volume was chest wall only in 5.6% of the cases. The volume was chest wall and supraclavicular fossa (SCL) in 20.3% of the cases; chest wall, SCL and internal mammary lymph node (IMN) in 27.6% of the cases; chest wall, SCL and posterior axillary lymph node in 25.9% of the cases; chest wall, SCL, IMN, and posterior axillary lymph node in 19.9% of the cases. Two patients received IMN only. The method of chest wall irradiation was tangential field in 57.3% of the cases and electron beam in 42% of the cases. A bolus for the chest wall was used in 54.8% of the tangential field cases and 52.5% of the electron beam cases. The radiation dose to the chest wall was 45~59.4 Gy (median 50.4 Gy), to the SCL was 45~59.4 Gy (median 50.4 Gy), and to the PAB was 4.8~38.8 Gy, (median 9 Gy) CONCLUSION: Different and various treatment methods were used for radiotherapy of the breast cancer patients after mastectomy in each hospital. Most of treatment methods varied in the irradiation of the chest wall. A separate analysis for the details of radiotherapy planning also needs to be followed and the outcome of treatment is needed in order to evaluate the different processes.

Monte Carlo Calculation on the Dose Modulation Using Dynamic Magnetic Fields for 10 MV X-rays / 의학물리

Monte Carlo calculations were performed to demonstrate the dose modulation with dynamic magnetic fields in phantom. The goal of this study is to obtain the uniform dose distributions at a depth region as a target on the central axis of photon beam under moving transverse magnetic field. We have calculated the depth dose curves for two cases of moving magnetic field along a depth line, constant speed and optimal speed. We introduced step-by-step shift and time factor of the position of the electromagnet as an approximations of continuous moving. The optimal time factors as a function of magnetic field position were calculated by least square methods using depth dose data for static magnetic field. We have verified that the flat depth dose is produced by varying the speed of magnetic field as a function of position as a results of Monte Carlo calculations. For 3 T magnetic field, the dose enhancement was 10.1% in comparison to without magnetic field at the center of the target.

Phase II Study of Induction Irinotecan + Cisplatin Chemotherapy Followed by Concurrent Irinotecan + Cisplatin Plus Twice-Daily Thoracic Radiotherapy / 결핵및호흡기질환

BACKGROUND: Irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against small-cell lung cancer. Irinotecan also can act as a potential radiation sensitizer along with cisplatin. To evaluate efficacy and toxicity of irinotecan plus cisplatin (IP) with concurrent thoracic radiotherapy, we conducted a phase II study of IP followed by concurrent IP plus hyperfractionated thoracic radiotherapy in patients with previously untreated limited-stage small-cell lung cancer. METHODS: Twenty-four patients with previously untreated small-cell lung cancer were enrolled onto the study since November 2004. Irinotecan 60 mg/m2 was administered intravenously on days 1 and 8 in combination with cisplatin 60 mg/m2 on day1 every 21 days. From the first day of third cycle, twice-daily thoracic irradiation (total 45 Gy) was given. Prophylactic cranial irradiation was given to the patients who showed complete remission after concurrent chemoradiotherapy. Restaging was done after second and sixth cycle with chest CT and/or bronchosocpy. RESULTS: Up to November 2004, 19 patients were assessable. The median follow-up time was 12.5 months. A total of 99 cycles (median 5.2 cycles per patient) were administered. The actual dose intensity values were cisplatin 19.6 mg/m2/week and irinotecan 38.2 mg/m2/week. Among the 19 patients, the objective response rate was 95% (19 patients), with 9 patients (47%) having a complete response (CR). The major grade 3/4 hematological toxicities were neutropenia (35% of cycles), anemia (7% of cycles), thrombocytopenia (7% of cycles). Febrile neutropenia was 4% of cycles. The predominant grade 3/4 non-hematological toxicities was diarrhea (5% of cycles). Toxicities was not significantly different with concurrent administration of irinotecan and cisplatin with radiotherapy, except grade 3/4 radiation esophagitis (10% of patients). No treatment-related deaths were observed. The 1-year and 2-year survival rate of eligible patients was 89% (16/18) and 47% (9/18), respectively. CONCLUSION: Three-week schedule of irinotecan plus cisplatin followed by concurrent IP plus hyperfractionated thoracic radiotherapy is an effective treatment for limited disease small-cell lung cancer, with acceptable toxicity.

Phase II Study of Induction Irinotecan + Cisplatin Chemotherapy Followed by Concurrent Irinotecan + Cisplatin Plus Twice-Daily Thoracic Radiotherapy / 결핵및호흡기질환

BACKGROUND: Irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against small-cell lung cancer. Irinotecan also can act as a potential radiation sensitizer along with cisplatin. To evaluate efficacy and toxicity of irinotecan plus cisplatin (IP) with concurrent thoracic radiotherapy, we conducted a phase II study of IP followed by concurrent IP plus hyperfractionated thoracic radiotherapy in patients with previously untreated limited-stage small-cell lung cancer. METHODS: Twenty-four patients with previously untreated small-cell lung cancer were enrolled onto the study since November 2004. Irinotecan 60 mg/m2 was administered intravenously on days 1 and 8 in combination with cisplatin 60 mg/m2 on day1 every 21 days. From the first day of third cycle, twice-daily thoracic irradiation (total 45 Gy) was given. Prophylactic cranial irradiation was given to the patients who showed complete remission after concurrent chemoradiotherapy. Restaging was done after second and sixth cycle with chest CT and/or bronchosocpy. RESULTS: Up to November 2004, 19 patients were assessable. The median follow-up time was 12.5 months. A total of 99 cycles (median 5.2 cycles per patient) were administered. The actual dose intensity values were cisplatin 19.6 mg/m2/week and irinotecan 38.2 mg/m2/week. Among the 19 patients, the objective response rate was 95% (19 patients), with 9 patients (47%) having a complete response (CR). The major grade 3/4 hematological toxicities were neutropenia (35% of cycles), anemia (7% of cycles), thrombocytopenia (7% of cycles). Febrile neutropenia was 4% of cycles. The predominant grade 3/4 non-hematological toxicities was diarrhea (5% of cycles). Toxicities was not significantly different with concurrent administration of irinotecan and cisplatin with radiotherapy, except grade 3/4 radiation esophagitis (10% of patients). No treatment-related deaths were observed. The 1-year and 2-year survival rate of eligible patients was 89% (16/18) and 47% (9/18), respectively. CONCLUSION: Three-week schedule of irinotecan plus cisplatin followed by concurrent IP plus hyperfractionated thoracic radiotherapy is an effective treatment for limited disease small-cell lung cancer, with acceptable toxicity.

Radiation Induced Changes in the Expression of Fibronectin, Pai-1, MMP in Rat Glomerular Epithelial Cell / 대한방사선종양학회지

PURPOSE: Renal irradiation can lead to the development of radiation nephropathy, and this is characterized by the accumulation of extracellular matrix and final fibrosis. To determine the possible role of the glomerular epithelial cell, the radiation-induced changes in the expression of its genes associated with the extracellular matrix were analyzed. MATERIALS AND METHODS: Rat glomerular epithelial cells (GEpC) were irradiated with a single dose of 0, 2, 5, 10 and 20 Gy with using 6 MV LINAC (Siemens, USA), and the samples were collected 6, 24, 48 and 72 hours post-irradiation, respectively. Northern blotting, western blotting and zymography were used to measure the expression level of fibronectin (Fn), plasminogen activator inhibitor-1 (Pai-1), matrix metalloproteinases-2, 9 (MMP-2, 9), tissue inhibitor of metalloproteinase-2 (TIMP-2), tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). RESULTS: Irradiation with a single dose of 10 Gy resulted in a significant increase in Fn mRNA since 24 hours post-irradiation, and a single dose of 5 and 10 Gy significantly increased the Fn immunoreactive protein measured 48 hours post-irradiation. An increase in Pai-1 mRNA and protein was also observed and especially, a single dose of 10 Gy significantly increased the mRNA measured 24 and 48 hours post-irradiation. The active MMP-2 measured 24 hours post-irradiation slightly increased in a dose dependent manner, but this increase did not reach statistical significance. The levels of MMP-9, TIMP-2, t-PA and u-PA appeared unaltered after irradiation. CONCLUSION: Irradiation of the glomerular epithelial cells altered the expression of genes associated with the extracellular matrix, implying that the glomerular epithelial cell may be involved in the development of radiation nephropathy.

Changes of Apoptosis After X-irradiation During the Hindlimb Development in the Rat Fetus / 체질인류학회지

Ionizing radiation exerts harmful effect during the limb development, but the exact mechanism is still largely unknown. In this study, 2 Gy of X-ray irradiated to the rat fetuses on gestation day of 13.7 when the hindlimb buds appear, and sacrificed at GD 14.7, GD 15.7 and GD 16.7, respectively. To reveal the changes of apoptotic figures between control and experimental groups, TUNEL immunohistochemistry and confocal laser scanning microscopy were carried. Mean body weight of fetuses of irradiated groups were decreased significantly compared to the control group. Numerical digit anomalies and asymmetries between right and left sides were increased significantly in the irradiated group compared to control group. Some digit anomalies were increased significantly in the right side. Radiation-induced decrement of the density of apoptotic figures on GD 14.7 was presumed to be related with foot and digit anomalies.

Comparison of the Efficacy of Oral Capecitabine versus Bolus 5-FU in Preoperative Radiotherapy of Locally Advanced Rectal Cancer

The effects of treatment with oral capecitabine vs. bolus 5-FU, administered concurrently with preoperative radiotherapy, were compared in the treatment of locally advanced rectal cancer (LARC). One hundred and twenty-seven patients with LARC received concurrent preoperative chemoradiation using two cycles bolus 5-FU (500 mg/m2/day) plus leucovorin (LV, 20 mg/m2/day) (Group I). Another LARC group received concurrent chemoradiation using two cycles 1,650 mg/m2/day of oral capecitabine and 20 mg/m2/day of LV (Group II, 97 patients). Radiation was delivered to the primary tumor at 50.4 Gy in both groups. Definitive surgery was performed 6 weeks after the completion of chemoradiation. A pathologic complete remission was achieved in 11.4% of patients in Group I and in 22.2% of patients in Group II (p= 0.042). The down-staging rates of the primary tumor and lymph nodes were 39.0/ 68.7% in Group I and 61.1/87.5% in Group II (p=0.002/0.005). Sphincter-preserving surgery was possible in 42.1% of patients in Group I and 66.7% of those in Group II (p=0.021). Grade 3 or 4 leucopenia, diarrhea, and radiation dermatitis were statistically more prevalent in Group I than in Group II, while the opposite was true for grade 3 hand-foot syndrome. Preoperative chemoradiation using oral capecitabine was better tolerated than bolus 5-FU and was more effective in the promotion of both down-staging and sphincter preservation in patients with LARC.

Twice Daily Radiation Therapy Plus Concurrent Chemotherapy for Limited-Stage Small Cell Lung Cancer / 대한방사선종양학회지

PURPOSE: A retrospective study was performed to evaluate the efficiency and feasibility of twice daily radiation therapy plus concurrent chemotherapy for limited-stage small cell lung cancer in terms of treatment response, survival, patterns of failure, and acute toxicities. MATERIALS AND METHODS: Between February 1993 and October 2002, 76 patients of histologically proven limited-stage small cell lung cancer (LS-SCLC) were treated with twice daily radiation therapy and concurrent chemotherapy. Male was in 84% (64/76), and median age was 57 years (range, 32~75 years). Thoracic radiation therapy consisted of 120 or 150 cGy per fraction, twice a day at least 6 hours apart, 5 days a week. Median total dose was 50.4 Gy (range, 45~51 Gy). Concurrent chemotherapy consisted of CAV (cytoxan 1000 mg/m2, adriamycin 40 mg/m2, vincristine 1 mg/m2) alternating with PE (cisplatin 60 mg/m2, etoposide 100 mg/m2) or PE alone, every 3 weeks. The median cycle of chemotherapy was six (range, 1~9 cycle). Prophylactic cranial irradiation (PCI) was recommended to the patients who achieved a complete response (CR). PCI scheme was 25 Gy/ 10 fractions. Median follow up was 18 months (range, 1~136 months). RESULTS: Overall response rate was 86%; complete response in 39 (52%) and partial response in 26 (34%) patients. The median overall survival was 23 months. One, two, and three year overall survival rate was 72%, 50% and 30%, respectively. In univariate analysis, the treatment response was revealed as a significant favorable prognostic factor for survival (p<0.001). Grade 3 or worse acute toxicities were leukopenia in 46 (61%), anemia in 5 (6%), thrombocytopenia in 10 (13%), esophagitis in 5 (6%), and pulmonary toxicity in 2 (2%) patients. Of 73 evaluable patients, 40 (55%) patients subsequently had disease progression. The most frequent first site of distant metastasis was brain. CONCLUSION: Twice daily radiation therapy plus concurrent chemotherapy produced favorable response and survival for LS-SCLC patients with tolerable toxicities. To improve the treatment response, which proved as a significant prognostic factor for survival, there should be further investigations about fractionation scheme, chemotherapy regimens and compatible chemoradiotherapy schedule.

Treatment Outcomes of Three-Dimensional Conformal Radiotherapy for Stage III Non-Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To evaluate the treatment outcomes of the three-dimensional conformal radiotherapy (3D-CRT), in conjunction with induction chemotherapy, for the treatment of stage III non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Between November 1998 and March 2003, 22 patients with histologically proven, clinical stage III NSCLC, treated with induction chemotherapy, followed by 3D-CRT, were retrospectively analyzed. There were 21 males (96%) and 1 female (4%), with a median age of 68.5 (range, 42~79). The clinical cancer stages were IIIA and IIIB in 41 and 59%, respectively. The histologies were squamous cell carcinoma, adenocarcinoma and others in 73, 18 and 9%, respectively. Twenty patients (91%) received induction chemotherapy before radiation therapy. The majority of the chemotherapy regimen consisted of cisplatin and gemcitabine. Radiation was delivered with conventional anteroposterior/ posteroanterior fields for 36 Gy, and then 3D-CRT was performed. The total radiation dose was 70.2 Gy. The median follow-up period was 17 months (range, 4~59 months). RESULTS: The median overall survival was 19 months. The two and four-year overall survival rates were 37.9 and 30.3%, respectively. The median progression-free survival was 21 months. The two and four-year progression-free survival rates were 42.1 and 21%, respectively. The prognostic factors for overall survival by a univariate analysis were age, histology and T stage (p<0.05). Acute radiation toxicities, as evaluated by the RTOG toxicity criteria, included two cases of grade 3 lung toxicity and one case of grade 2 esophagus toxicity. CONCLUSIONS: The radiation dose could be increased without a significant increment in the acute toxicities when using 3D-CRT. It also seems to be a safe, well- tolerated and effective treatment modality for stage III NSCLC.

Screening of Brain Metastasis with Limited Magnetic Resonance Imaging (MRI):Clinical Implications of Using Limited Brain MRI During Initial Staging for Non-small Cell Lung Cancer Patients

The purpose of this prospective study was to determine whether using magnetic resonance imaging (MRI) for early screening for brain metastases (BM) can improve quality of life, survival in patients with non-small cell lung cancer (NSCLC). The study group comprised 183 patients newly diagnosed with NSCLC. All patients underwent limited brain MRI and routine workups. The control group comprised 131 patients with NSCLC who underwent limited brain MRI only if they had neurologic symptoms. The incidence of BM was 20.8% (38/183) in the study group and 4.6% (6/131) in the control group. The rate of upstaging based on the MRI data was 13.5% (15/111) overall and 15.9% (11/69) in patients that had been considered initially to be resectable surgically. There was no significant difference in survival outcome between the groups. Patients who had BM alone had a greater overall survival time (49 weeks) than those who had multiple systemic metastases (27 weeks; p=0.0307). In conclusions, limited brain MRI appears to be a useful, costeffective method to screen for BM at the time of initial staging. And it may facilitate timely treatment of patients with NSCLC and improve their survival and quality of life.