• Radiation Oncology Journal
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• v.27 no.4
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• pp.189-193
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• 2009

Purpose: To report on the changes in the patterns of care and survival over time for esthesioneuroblastoma. Materials and Methods: We retrospectively analyzed 42 previously untreated and histologically confirmed esthesioneuroblastoma patients seen between March 1989 and June 2007. According to Kadish's classification, 3 patients (7%) were stage A, 6 (14%) at stage B, and 33 (79%) at stage C. Of the 33 Kadish C patients, 19 and 14 patients were treated from 1989 through 2000 and from 2001 through 2007, respectively. Treatment included surgical resection, radiotherapy, chemotherapy, or a combination of these methods. Chemotherapy was administered to 8 of 19 patients (42%) seen from 1989 through 2000, whereas all of the 14 patients seen from 2001 through 2007 received chemotherapy (p<0.001). No patient was treated by three-dimensional conformal radiotherapy (3D-CRT) from 1989 through 2000, however 8 of 14 patients (67%) seen from 2001 through 2007 underwent 3D-CRT (p<0.001). The median follow-up time for surviving patients was 6.5 years (range, 2.2~15.8 years). Results: The 5-year overall survival (OS) and progression-free survival (PFS) rates for the entire cohort were 53% and 39%, respectively. The 5-year OS was 100% for Kadish stages A or B and 39% for stage C (p=0.007). For patients with stage C disease who were treated from 1989 to 2000 and from 2001 to 2007, the 5-year OS rate was 26% and 59% (p=0.029), respectively and the corresponding 5-year PFS rate was 16% and 46% (p=0.001), respectively. Intraorbital extension and treatment era (1989~2000 vs. 2001~2007) were found as independent factors for OS and PFS in a multivariate analyses. Conclusion: The results of this study suggest that treatment era, which features a distinction in treatment modality and technique with the introduction of 3D-CRT, may be the cause of improved OS and PFS in Kadish stage C patients. To achieve better outcomes for patients with Kadish stage C, combined chemoradiotherapy, especially 3D-CRT, is recommended in addition to surgery.

• Radiation Oncology Journal
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• v.27 no.3
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• pp.153-162
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• 2009

Purpose: To evaluate the long-term results after breast-conserving surgery and radiation therapy in early breast cancer in terms of failure, survival, and cosmesis. Materials and Methods: One hundred fifty-four patients with stage I and II breast cancer were treated with conservative surgery plus radiotherapy between January 1992 and December 2002 at the Keimyung University Dongsan Medical Center. According to TNM stage, 93 patients were stage I, 50 were IIa, and 11 were IIb. The affected breasts were irradiated with 6 MV photons to 50.4 Gy in 28 fractions over 5.5 weeks with a boost irradiation dose of 10~16 Gy to the excision site. Chemotherapy was administered in 75 patients and hormonal therapy in 92 patients with tamoxifen. Follow-up periods were 13~179 months, with a median of 92.5 months. Results: The 5- and 10-year overall survival rates were 97.3% and 94.5%, respectively. The 5- and 10-year disease-free survival (5YDFS and 10YDFS, respectively) rates were 92.5% and 88.9%, respectively; the ultimate 5YDFS and 10YDFS rates after salvage treatment were 93.9% and 90.2%, respectively. Based on multivariate analysis, only the interval between surgery and radiation therapy ($\leq$6 weeks vs. >6 weeks, p=0.017) was a statistically significant prognostic factor for DFS. The major type of treatment failure was distant failure (78.5%) and the most common distant metastatic site was the lungs. The cosmetic results were good-to-excellent in 96 patients (80.7%). Conclusion: Conservative surgery and radiation for early stage invasive breast cancer yielded excellent survival and cosmetic results. Radiation therapy should be started as soon as possible after breast-conserving surgery in patients with early breast cancer, ideally within 6 weeks.

• Radiation Oncology Journal
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• v.25 no.4
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• pp.193-200
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• 2007

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 $I{\sim}IVa$ esophageal squamous cell carcinoma were selected for this study. Radiotherapy was administered with daily $1.8{\sim}2\;Gy$ 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.

• Journal of Chest Surgery
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• v.36 no.2
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• pp.91-97
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• 2003

With the advent of stage-adapted multimodal regiments for esophageal malignancy, accurate staging has become of utmost importance. Endoscopic ultrasono graphy(EUS) i.: a diagnostic method for the local staging of esophageal cancer, in particular for T and N evaluation. The aim of this study was to examine the diagnostic efficacy of the EUS and to evaluate the relation between prognosis and EUS findings. Material and Method : We reexamined the cases of 88 consecuitive patients who underwent transthroacic esophagectomy and cervical esophagogastrostomy for esophageal cancer from January 1991 to July 2001 We compared EUS findings, histological results and outcomes. Result : There were 83 male(94.3%) and 5 female. Median age was 61.3 years old. Overall staging accuracy were 59.0% for T staging and 76.0% for N staging, In early T staging group, the accuracy was 74.9% except 74 stage. However significant differences were not found in the ability of EUS-determined T-stage and N-Stage to predict survival. Multivariate analysis showed EUS-stage to predict survival. Conclusion : EUS provides a high degree of accuracy in assessing both T and N parameters in staging esophagal cancer. EUS should be performed in all patients with esophageal cancer, not only for staging before therapy, but also as a valuable method of determining prognosis.

• Tuberculosis and Respiratory Diseases
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• v.53 no.3
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• pp.309-318
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• 2002

Background : Usual interstitial pneumonia (UIP) is a fatal progressive fibrotic disorder of the lung with unknown etiology and characterized by a poor response to conventional immunosuppressive therapy. The histologic hallmark of UIP is parchy distribution of subpleural fibrosis and fibroblastic foci(FBF) with interposed normal appearing lung. Because FBF is a collection of actively proliferating myofibroblasts, it can be a marker of activity and prognosis of UIP. However, there were contradictory reports about the correlation between the degree of FBF and survival. Therefore we performed this study to investigate the value of FBF as prognostic marker of UIP. Methods : This was a retrospective study on the 46 patients(M:F=33:13, mean age:$59{\pm}12$ years) with UIP diagnosed by the surgical lung biopsy at the Asan Medical Center, Seoul, Korea between 1990 and 2000 and had follow-up of more than a year. All the biopsy specimens were reevaluated and diagnosed as UIP according to the ATS/ERS classification. Semiquantitative grading of FBF(absent, 0; mild 1; moderate 2; marked 3) by the experienced pathologists who did not know the clinical findings were compared to the clinical data and the follow up course. Results : Thirteen patients(28.2%) died of UIP progression during the study period. The median survival time of all the subjects was 26 months after the biopsy. At the univariate analysis, FVC, $D_Lco$, smoking history and the grade of FBF were significantly related to the survial. The survival was longer in subjects with lesser degrees of FBF, higher DLco, higher FVC and history of smoking. However the multivariate analysis with Cox regression test showed the extent of FBF was the only independent prognostic marker of UIP. Conclusion : These data suggested that the extent of FBF on the surgical lung biopsy can be used as a prognostic marker of UIP.

• Radiation Oncology Journal
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• v.24 no.3
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• pp.157-163
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• 2006

[ $\underline{Purpose}$ ]: To evaluate the role of postoperative adjuvant chemoradiotherapy in rectal cancer, we retrospectively analyzed the treatment outcome of patients with rectal cancer taken curative surgical resection and postoperative adjuvant chemoradiotherapy. $\underline{Materials\;and\;Methods}$: A total 46 patients with AJCC stage II and III carcinoma of rectum were treated with curative surgical resection and postoperative adjuvant chemoradiotherapy. T3 and T4 stage were 38 and 8 patients, respectively. N0, N1, and N2 stage were 12, 16, 18 patients, respectively. Forty patients received bolus infusions of 5-fluorouracil ($500\;mg/m^2/day$) with leucovorin ($20\;mg/m^2/day$), every 4 weeks interval for 6 cycles. Oral Uracil/Tegafur on a daily basis for $6{\sim}12$ months was given in 6 patients. Radiotherapy with 45 Gy was delivered to the surgical bed and regional pelvic lymph node area, followed by $5.4{\sim}9\;Gy$ boost to the surgical bed. The follow up period ranged from 8 to 75 months with a median 35 months. $\underline{Results}$: Treatment failure occurred in 17 patients (37%). Locoregional failure occurred in 4 patients (8.7%) and distant failure in 16 patients (34.8%). There was no local failure only. Five year actuarial overall survival (OS) was 51.5% and relapse free survival (RFS) was 58.7%. The OS and RFS were 100%, 100% in stage N0 patients, 53.7%, 47.6% in N1 patients, and 0%, 41.2% in N2 patients (p=0.012, p=0.009). The RFS was 55%, 78.5%, and 31.2% in upper, middle, and lower rectal cancer patients, respectively (p=0.006). Multivariate analysis showed that N stage (p=0.012) was significant prognostic factor for OS and that N stage (p=0.001) and location of tumor (p=0.006) were for RFS. Bowel complications requiring surgery occurred in 3 patients. $\underline{Conclusion}$: Postoperative adjuvant chemoradiotherapy was an effective modality for locoregional control of rectal cancer. But further investigations for reducing the distant failure rate are necessary because distant failure rate is still high.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.265-276
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• 2000

Purpose : Between January 1983 and December 1988, 218 female Patients with known breast cancer and positive axillary nodes were treated with adjuvant radiotherapy and chemotherapy following radical mastectomy. Treatment results were retrospectively analysed at the Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University of College of Medicine. Materials and Methods : The patients were classified into 3 groups; group I included II patients treated with adjuvant chemotherapy alone; in group 2, 52 patients treated with radiotherapy alone; and in group 3, n patients treated with combined chemo-radiotherapy. The mean age was 44 years and ranged from 27 to 70. The median follow-up time was 51 months. Results :Seven-year relapse free and overall survival rates were 56$\%$ and 67$\%$; in group 1, 50$\%$ and 56$\%$ in group 2, 51$\%$ and 65$\%$ and in group 3, 62$\%$ and 75$\%$ respectively. This difference was not statistically significant(p<0.05). The loco-regional failure rates were 13$\%$ and distant failure rates were 33$\%$. There was less risk of loco-regional failure in group 2 and 3 which included radiotherapy (p<0.05). But there was no significantly difference in the rates of distant failure( p>0.05). By univariate analysis, the only significant prognostic factor affecting relapse-free survival was the percentage of positive axillary nodes; and the overall survival significantly correlated with the primary tumor site, the number or percentage of positive axillary nodes, and stage. But in multivariate analysis, the only significant prognostic factor was treatment modality. By univariate analysis of prognostic factors affecting the rates of overall failure and distant failure, the significant prognostic factors was the percentage of positive axillary nodes; and the risk of the loco-regional failure significantly correlated with the treatment modality. Conclusion :In conclusion, these results suggest a potential for decreasing the risk of loco-regional failure with the addition of postoperative radiotherapy to chemotherapy in the premenopausal patients, and in the patients with number or percentage of positive nodes more than 4 or 1/3. The results of this study suggest that the combined chemo-radiotherapy as adjuvant treatment following radical mastectomy was the most effective modaliw in groups of 2$\~$5 cm sized tumor, stage IIB, and in patients with more than 4 or 1/3 of number or percentage of positive nodes.

• Clinical and Experimental Pediatrics
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• v.49 no.2
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• pp.173-180
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• 2006

Purpose : Cytomegalovirus(CMV) infection still remains as a major cause of morbidity and mortality after stem cell transplantation. In this study, we analyzed the results of antigenemia-guided preemptive therapy among children with allogeneic hematopoietic stem cell transplantation to determine the incidence and risk factors associated with CMV antigenemia, and evaluated the efficacy of the CMV antigenemia based preemptive therapy. Methods : We enrolled 213 pediatric patients following allogeneic hematopoietic stem cell transplantation(HSCT), at the Catholic HSCT center between October 1998 and December 2003. Pre-emptive ganciclovir was started when more than 5 CMV Ag-positive cells were detected in matched sibling HSCT, and when any Ag-positive cells were seen in unrelated allogenic HSCT. Results : CMV antigenemia was observed in 88(41.3 percent) of 213 patients on median day 28(day 11-99). In univariated analysis, use of unrelated donors(other than siblings), age of recipient(more than 5 years at transplant) at transplantation, the presence of recipient CMV-IgG before transplantation, TBI-based conditioning regimen and the presence of acute GvHD(grade ${\geq}II$) were the risk factors for positive CMV antigenemia. In multivariate analysis, unrelated bone marrow transplantation, positive recipient CMV serology and acute GvHD(grade ${\geq}II$) were the independent risk factors for positive CMV antigenemia. Conclusion : Risk factors of CMV infection in children were CMV serostatus of the recipient, the source of stem cells, and acute graft-versus-host disease. The pre-emptive therapy based on CMV antigenemia was effective in the prevention of CMV disease.

• Radiation Oncology Journal
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• v.24 no.1
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• pp.30-36
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• 2006

Purpose: It is well known from clinical experience that acute complications of chemoradiation therapy vary from patients to patients. However, there are no known factors to predict these acute complications before treatment starts. The human XRCC1 gene is known as a DNA base excision repair gene. We investigated the possibilities of XRCC1 gene polymorphisms as a predictor for the acute complications of chemoradiation therapy in colorectal cancer patients. Materials and Methods: From July 1997 to June 2003, 86 colorectal cancer patients (71 rectal cancer, 13 sigmoid colon cancer and 2 colon cancer patients) were treated with chemoradiation therapy at the Department of Radiation Oncology, Inha University Hospital. Twenty-two patients were in stage B, 50 were in stage C, 8 were in stage D and 6 patients were unresectable cases. External radiation therapy was delivered with 10MV X-ray at a 1.8 Gy fraction per day for a total dose of radiation of $30.6{\sim}59.4 Gy$ (median: 54 Gy). All the patients received 5-FU based chemotherapy regimen. We analyzed the acute complications of upper and lower gastrointestinal tract based on the RTOG complication scale. The initial and lowest WBC and platelet count were recorded during both the RT period and the whole treatment period. Allelic variants of the XRCC1 gene at codons 194, 280 and 399 were analyzed in the lymphocyte DNA by performing PCR-RFLP. Statistical analyses were carried out with the SAS (version 6.12) statistical package. Results: When all the variables were assessed on the multivariate analysis, recurrent disease revealed the factors that significantly correlated with upper gastrointestinal acute complications. Arg399Gln polymorph isms of the XRCC1 gene, the radiation dose and the frequencies of chemotherapy during radiation therapy were significantly correlated with lower gastrointestinal complications. Arg399Gln polymorph isms also affected the decrease of the WBC and platelet count during radiation therapy. Conclusion: Although the present sample size was too small for fully evaluating this hypothesis, this study suggests that Arg399Gln polymorph isms of the XRCC1 genes may be used as one of the predictors for acute complications of chemoradiation therapy in colorectal cancer patients.

• Radiation Oncology Journal
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• v.28 no.2
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• pp.57-63
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• 2010

Purpose: We performed an immunohistochemical study with pre-treatment biopsy specimens to evaluate the prognostic significance of four biomolecular markers which can be used as a predictive assay for radiotherapy (RT) treatment of nasopharyngeal carcinoma (NPC). Materials and Methods: From January 1998 through December 2006, 68 patients were histologically diagnosed as non-metastatic NPC and treated by RT. Only 38 patients had the paraffin block for the immunohistochemical study. Thirty-one patients had undifferentiated carcinoma and 7 patients had squamous cell carcinoma. Thirtytwo patients (84%) had advanced stage NPC (2002 AJCC Stage III~IV). Immunohistochemical staining was performed for Met, COX-2, nm23-H1, and epidermal growth factor receptor (EGFR) expression using routine methods. Results: The median follow-up time was 30 months (range, 11 to 83 months) for all patients, and 39 months (range, 19 to 83 months) for surviving patients. The 5-year overall survival (OS) rate of the patients with high Met extent (${\geq}50%$) was significantly lower than that of the patients with low Met extent (48% vs. 84%, p=0.02). In addition, Met extent was also a significant prognostic factor in multivariate analysis (p=0.01). No correlation was observed between Met extent and T stage, N stage, stage group, gender, age, and the response to chemotherapy or RT. Met extent showed moderate correlation with COX-2 expression (Pearson coefficient 0.496, p<0.01), but COX-2 expression did not affect OS. Neither nm23-H1 or EGFR expression was a prognostic factor for OS in this study. Conclusion: High Met extent (${\geq}50%$) might be an independent prognostic factor that predicts poor OS in NPC treated with RT.