• Radiation Oncology Journal
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• v.12 no.1
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• pp.99-107
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• 1994

Among the 63 patients with histopathologically proven primary squamous cell anal cancer who were managed in Presbyterian Medical Center and Yonsei University Cancer from Jan. 1971 to Dec. 1991, 34 patients, who were managed with surgery alone(abdominoperineal resection) or post-operative radiotherapy and concurrent chemoradiotherapy were analysed. With mean follow up time of 81.3 months, 30 Patients(88$ \% $) were followed up from 17 to 243 months. In methods, 10 patients were treated with surgery alone. 9 Patients were treated with combined surgery and postoperative radiotherapy(50$\∼$60 Gy in 28$\∼$30 fractions). 15 patients were treated with concurrent chemoradiotherapy. Chemotherapy (Mitomycin C 15 mg/squ, bolus injection day 1;5-FU, 750 mg/squ, 24hr infusion, day 1 to 5) and radiotherapy started the same day. A dose of 30 Gy was given to the tumor and to the pelvis including inguinal nodes, in 15 fractions. After 2 weeks a boost of radiotherapy(20 Gy) to the ano-perineal area and second cycle of chemotherapy completed the treatment. The overall 5-year survival rate was 56.2$ \% $. Concurrent chemoradiotherapy group was 70$ \% $ and surgery alone group was 16.7$ \% $. According to the cox proportional harzard model, there was significant difference between survival with concurrent chemoradiotherapy and surgery alone(p=0.0129), but post-operative radiotherapy was 64.8$ \% $, which was not stastically significant(p=0.1412). In concurrent chemoradiotherapy group, the anal funtion Preservation rate was 87$ \% $ and the severe complication rate(grade 3 stenosis and incontinence) was 13.3$ \% $. In conclusion, we conclude that the concurrent chemoradiotherapy may be effective treatment modality in patients with anal cancer.

• Radiation Oncology Journal
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• v.20 no.1
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• pp.62-67
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• 2002

Purpose : This study was undertaken to analyze the efficacy and sphincter preservation rate of platinum based neoadjuvant chemotherapy Plus radiotherapy versus abdominoperineal resection and Postoperative radiotherapy for anal cancer. Materials and Methods : Data of forty-two patients with anal cancer were retrospectively analyzed. Among thirty-eight patients with epidermoid histology, four patients received radiotherapy, and nineteen patients received abdominoperineal resection and adjuvant radiotherapy with or without chemotherapy $(APR+RT{\pm}CT)$, and fifteen patients received neoadjuvant chemotherapy and radiotherapy (CRT). The CRT regimen was composed of three cycles of 5-fluorouracil $(1,000\;mg/m^2\;bolus\;on\;D1\~5)$ and cisplatin $(60\;mg/m^2\;bolus\;on\;D1)$ followed by 50.4 Gy to the tumor bed and regional lymphatics over 5.5 weeks. Both inguinal lymphatics were treated with an identical dose schedule. Residual disease was treated with an additional three cycles of identical adjuvant chemotherapy. An identical dose schedule was used for post-operative radiotherapy. Median follow-up period was eighty-five months. Results : Overall five-year survival rates were $80.3\%$, 88.9 and $79.4\%$ for entire patients, $APR+RT{\pm}CT$ group, and the CRT group, respectively. No significant difference was found between the two groups (p=0.49). Anus preservation rate for the CRT group was $86.7\%$. Age (0=0.0164) and performance status (p=0.0007) were found to be significant prognostic factors by univariate analysis. Age (p=0.0426), performance status (p=0.0008), and inguinal lymph node metastasis (e=0.0093) were statistically significant prognostic factors by multivariate analysis. No case of RTOG grade 3 complication or higher was reported. Conclusion : This and other recent studies have shown that combined chemotherapy plus radiotherapy for anal cancer results in a high rate of anal sphincter preservation as well as local control and survival. Furthermore, neoadjuvant use of chemotherapy with a cisplatin based regimen rather than a concurrent regimen may lead to a decrease in complications.

• Radiation Oncology Journal
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• v.35 no.3
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• pp.198-207
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• 2017

Purpose: Whether preoperative chemoradiotherapy (CRT) is better than postoperative CRT in oncologic outcome and toxicity is contentious in prospective randomized clinical trials. We systematically analyze and compare the treatment result, toxicity, and sphincter preservation rate between preoperative CRT and postoperative CRT in stage II-III rectal cancer. Materials and Methods: We searched Medline, Embase, and Cochrane Library from 1990 to 2014 for relevant trials. Only phase III randomized studies performing CRT and curative surgery were selected and the data were extracted. Meta-analysis was used to pool oncologic outcome and toxicity data across studies. Results: Three randomized phase III trials were finally identified. The meta-analysis results showed significantly lower 5-year locoregional recurrence rate in the preoperative-CRT group than in the postoperative-CRT group (hazard ratio, 0.59; 95% confidence interval, 0.41-0.84; p = 0.004). The 5-year distant recurrence rate (p = 0.55), relapse-free survival (p = 0.14), and overall survival (p = 0.22) showed no significant difference between two groups. Acute toxicity was significantly lower in the preoperative-CRT group than in the postoperative-CRT group (p < 0.001). However, there was no significant difference between two groups in perioperative and chronic complications (p = 0.53). The sphincter-saving rate was not significantly different between two groups (p = 0.24). The conversion rate from abdominoperineal resection to low anterior resection in low rectal cancer was significantly higher in the preoperative-CRT group than in the postoperative-CRT group (p < 0.001). Conclusions: As compared to postoperative CRT, preoperative CRT improves only locoregional control, not distant control and survival, with similar chronic toxicity and sphincter preservation rate in rectal cancer patients.

• Radiation Oncology Journal
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• v.36 no.1
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• pp.17-24
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• 2018

Purpose: This study aimed to assess complications and outcomes of a new approach, that is, combining short course radiotherapy (SRT), concurrent and consolidative chemotherapies, and delayed surgery. Materials and Methods: In this single arm phase II prospective clinical trial, patients with T3-4 or N+ M0 rectal adenocarcinoma were enrolled. Patients who received induction chemotherapy or previous pelvic radiotherapy were excluded. Study protocol consisted of three-dimensional conformal SRT (25 Gy in 5 fractions in 1 week) with concurrent and consolidation chemotherapies including capecitabine and oxaliplatin. Total mesorectal excision was done at least 8 weeks after the last fraction of radiotherapy. Primary outcome was complete pathologic response and secondary outcomes were treatment related complications. Results: Thirty-three patients completed the planned preoperative chemoradiation and 26 of them underwent surgery (24 low anterior resection and 2 abdominoperineal resection). Acute proctitis grades 2 and 3 were seen in 11 (33.3%) and 7 (21.2%) patients, respectively. There were no grades 3 and 4 subacute hematologic and non-hematologic (genitourinary and peripheral neuropathy) toxicities and perioperative morbidities such as anastomose leakage. Grade 2 or higher late toxicities were observed among 29.6% of the patients. Complete pathologic response was achieved in 8 (30.8%) patients who underwent surgery. The 3-year overall survival and local control rates were 65% and 94%, respectively. Conclusion: This study showed that SRT combined with concurrent and consolidation chemotherapies followed by delayed surgery is not only feasible and tolerable without significant toxicity but also, associated with promising complete pathologic response rates.

• Radiation Oncology Journal
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• v.9 no.1
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• pp.93-102
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• 1991

To evaluate the role of postoperative pelvic radiation therapy in rectal cancer, a retrospective analysis was done on 189 patients with modified Astler-Coiler stages B2+3, Cl , and C2+3 who were treated from February 1979 to June 1980. Forty-seven patients were staged as B2+3,17 as Cl, and 125 as C2+3. As a curative resection,41 received low anterior resection,143 received abdomino-perineal resection, and five received pelvic exenteration. The survival and disease-free survival rates of the total patients at five year were $45.3\%\;and\;44.1\%$, respectively. The stage was an important prognostic factor for survival and disease-free survival: the survival rates at five year were $63.4\%$ in stage B2+3, $62.4\%$ in C1, and $37.2\%$ in C2+3 (p<0.005): the disease-free survival rates at five year were $55.7\%$ in B2+3, $65.7\%$ in C1, and $30.4\%$ in C2+3, respectively (p<0.01). The liver was the most frequently involved organ of recurrence followed by the lung and the perineum. The patients who received low anterior resection achieved better disease-free survival but were more prone to late radiation bowel morbidities than those who received abdominoperineal resection. Postperative Pelvic radiation therapy Proved to be effective in locoregional disease control but did not prevent the appearance of distant metastasis, which was of major concern in advanced stages. Patterns of treatment failure, and factros relating to radiation morbidity are discussed, and therapeutic options for better results are proposed.

• Radiation Oncology Journal
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• v.24 no.1
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• pp.21-29
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• 2006

Purpose: This study explored the anal sphincter-saving rate and down-staging rate after preoperative chemoradiotherapy for treating lower rectal cancer. We also explored the prognosis of the patients who refused surgery after preoperative chemoradiotherapy. Materials and Methods: Thirty seven patients with histologically proven lower rectal cancer who underwent preoperative chemoradiotherapy were retrospectively analyzed. In each case, the tumor location was 0 to 5 em from the anal verge, and curative resection of the cancer with performing a sphincter-saving procedure was not feasible before chemoradiotherapy. In each case, the staging examinations, including biopsy, were done before starting radiotherapy and this was repeated at 1 month after radiation therapy. Results: After chemoradiotherapy, among the 37 included patients, 56.8% and 32.4% were downstaged to the T stage and N stage, respectively, when comparing the postradiotherapy stage with pre-radiotherapy stage. Twenty five patients underwent complete resection of cancer at 6 weeks after radiotherapy: eleven, eight and six patients underwent abdominoperineal resection, low anterior resection and local excision, respectively. The sphincter-saving rate among the 24 completely resected cases was 54.2%. Twelve patients refused surgery after radiotherapy. Among 6 patients who refused surgery with biopsy-proven complete remission after chemoradiotherapy, 5 patients were alive without disease at a median follow up period of 31 months, and only 1 patient had local failure. Conclusion: For lower rectal cancer, a high sphincter-saving rate was accomplished with preoperative chemoradiotherapy. The prognosis of the patients who refused surgery with biopsy proven complete remission after chemoradiotherapy was good and these patients need to be kept under close surveillance.

• Radiation Oncology Journal
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• v.27 no.2
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• pp.78-83
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• 2009

Purpose: To examine the effect of suboptimal chemotherapy in patients undergoing preoperative chemoradiotherapy for the treatment of rectal cancer. Materials and Methods: The medical records of 43 patients who received preoperative concurrent chemoradiotherapy, followed by radical surgery for the treatment of pathologically proven adenocarcinoma of the rectum from April 2003 to April 2006 were retrospectively reviewed. The delivered radiation dose ranged from 41.4 to 50.4 Gy. The standard group consisted of patients receiving two cycles of a 5-FU bolus injection for three days on the first and fifth week of radiotherapy or twice daily with capecitabine. The standard group included six patients for each regimen. The non-standard group consisted of patients receiving one cycle of 5-FU bolus injection for three days on the first week of radiotherapy. The non-standard group included 31 patients. Radical surgery was performed at a median of 58 days after the end of radiotherapy. A low anterior resection was performed in 36 patients, whereas an abdominoperineal resection was performed in 7 patients. Results: No significant difference was observed between the groups with respect to pathologic responses ranging from grades 3 to 5 (83.3% vs. 67.7%, p=0.456), downstaging (75.0% vs. 67.7%, p=0.727), and a radial resection margin greater than 2 mm (66.7% vs. 83.9%, p=0.237). The sphincter-saving surgery rate in low-lying rectal cancers was lower in the non-standard group (100% vs. 75%, p=0.068). There was no grade 3 or higher toxicity observed in all patients. Conclusion: Considering that the sphincter-saving surgery rate in low-lying rectal cancer was marginally lower for patients treated with non-standard, suboptimal chemotherapy, and that toxicity higher than grade 2 was not observed in the both groups, suboptimal chemotherapy should be avoided in this setting.

• Radiation Oncology Journal
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• v.17 no.1
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• pp.36-41
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• 1999

Purpose : We reviewed the treatment results for the patients with locally recurrent rectal carcinoma. The object was to evaluate the treatment outcome and to identify the prognostic factors influencing the survival. Methods and Materials: Twenty-eight patients with locally recurrent rectal carcinoma treated principally with external-beam radiation therapy between 1982 to 1996 in the Department of Radiation Oncology at Paik and Hanyang Hospital were reviewed retrospectively Of these, 17 patients had initially abdominoperineal resection, 9 had low anterior resection, and 2 had local excision. No patients had received adjuvant radiation therapy for the primary disease. There were 14 men and 14 women whose ages ranged from 31 to 72 years (median age:54.5). Median time from initial surgery to the start of radiation therapy for local recurrence was 11 months (4~47 months). Radiation therapy was given with total doses ranging from 27 to 64.8 Gy (median=51.2 Gy). Results : The median survival was 16.7 months. The 2-year and 5-year survival rates were 20.1%, 4.1% respectively. Upon multivariate analysis, overall survival was positively correlated with duration of intervals from initial surgery to local recurrence (P=0.039). Relief of pelvic symptoms was achieved in 17 of 28 patients (60.7%). Pain and bleeding responded in 40% and 100% of patients, respectively Conclusions : Patients with locally recurrent rectal carcinoma treated with radiotherapy have benefited symptomatically, and might have increased survivals with a small chance of cure. But, patient were rarely cured (median survival : 10 months, 5-year survival : less than 5%). Overall survival was positively correlated with long intervals from initial surgery to local recurrence. Future efforts should be directed to the use of effective therapy for patients with locally recurrent rectal carcinoma and adjuvant therapy for patients with rectal cancer to reduce the incidence of pelvic recurrence.

• Radiation Oncology Journal
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• v.20 no.3
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• pp.221-227
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• 2002

Purpose : To evaluate the role of postoperative chemoradiotherapy in locally advanced rectal cancer, we retrospectively analyzed the treatment results of patients treated by curative surgical resection and postoperative chemoradiotherapy. Materials and Methods : From April 1989 through December 1998, 119 patients were treated with curative surgery and postoperative chemoradiotherapy for rectal carcinoma in Gyeongsang National University Hospital. Patient age ranged from 32 to 73 years, with a median age of 56 years. Low anterior resection was peformed in 59 patients, and abdominoperineal resection in 60. Forty-three patients were AJCC stage II and 76 were stage III. Radiation was delivered with 6 MV X rays using either AP-PA two fields, AP-PA both lateral four fields, or PA both lateral three fields. Total radiation dose ranged from 40 Gy to 56 Gy. In 73 patients, bolus infusions of 5-FU $(400\;mg/m^2)$ were given during the first and fourth weeks of radiotherapy. After completion of radiotherapy, an additional four to six cycles of 5-FU were given. Oral 5-FU (Furtulone) was given for nine months in 46 patients. Results : Forty $(33.7\%)$ of the 119 patients showed treatment failure. Local failure occurred in 16 $(13.5\%)$ patients, 1 $(2.3\%)$ of 43 stage II patients and 15 $(19.7\%)$ of 76 stage III patients. Distant failure occurred in 31 $(26.1\%)$ patients, among whom 5 $(11.6\%)$ were stage II and 26 $(34.2\%)$ were stage III. Five-year actuarial survival was $56.2\%$ overall, $71.1\%$ in stage II patients and $49.1\%$ in stage III patients (p=0.0008). Five-year disease free survival was $53.3\%$ overall, $68.1\%$ in stage II and $45.8\%$ in stage III (p=0.0006). Multivariate analysis showed that T stage and N stage were significant prognostic factors for five year survival, and that T stage, N stage, and preoperative CEA value were significant prognostic factors for five year disease free survival. Bowel complication occurred in 22 patients, and was treated surgically in 15 $(12.6\%)$, and conservatively in 7 $(5.9\%)$. Conclusion : Postoperative chemoradiotherapy was confirmed to be an effective modality for local control of rectal cancer, but the distant failure rate remained high. More effective modalities should be investigated to lower the distant failure rate.

• Radiation Oncology Journal
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• v.27 no.4
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• pp.210-217
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• 2009

Purpose: To assess the influence of cyclooxygenase-2 (COX-2) expression on the survival of patients with a combination of rectal cancer and lymph node metastasis. Materials and Methods: The study included rectal cancer patients treated by radical surgery and postoperative radiotherapy at the Dong-A university hospital from 1998 to 2004. A retrospective analysis was performed on a subset of patients that also had lymph node metastasis. After excluding eight of 86 patients, due to missing tissue samples in three, malignant melanoma in one, treatment of gastric cancer around one year before diagnosis in one, detection of lung cancer after one year of diagnosis in one, liver metastasis in one, and refusal of radiotherapy after 720 cGy in one, 78 patients were analyzed. The immunohistochemistry for COX-2 was conducted with an autostainer (BenchMark; Ventana, Tucson, AZ, USA). An image analyzer (TissueMine; Bioimagene, Cupertino, CA, USA) was used for analysis after scanning (ScanScope; Aperio, Vista, CA, USA). A survival analysis was performed using the Kaplan Meier method and significance was evaluated using the log rank test. Results: COX-2 was stained positively in 62 patients (79.5%) and negatively in 16 (20.5%). A total of 6 (7.7%), 15 (19.2%), and 41 (52.6%) patients were of grades 1, 2, and 3, respectively for COX-2 expression. No correlation was found between being positive of COX-2 patient characteristics, which include age (<60-year old vs. $\geq$60), sex, operation methods (abdominoperineal resection vs. lower anterior resection), degrees of differentiation, tumor size (<5 cm vs. $\geq$5 cm), T stages, N stages, and stages (IIIa, IIIb, IIIc). The 5-year overall and 5-year disease free survival rates for the entire patient population were 57.0% and 51.6%, respectively. The 5-year overall survival rates for the COX-2 positive and negative patients were 53.0% and 72.9%, respectively (p=0.146). Further, the 5-year disease free survival rates for the COX-2 positive and negative patients were 46.3% and 72.7%, respectively (p=0.118). The 5-year overall survival rates were significantly different (p<0.05) for the degree of differentiation, N stage, and stage, whereas the 5-year disease free survival rates were significant for N stage and stage. Conclusion: Being positive for and the degree of COX-2 expression did not have a significant influence on the survival of rectal cancer patients with lymph node metastasis. However, N stage and stage did significantly influence the rateof survival. Further analysis of a greater sample size is necessary for the verification of the effect of COX-2 expression on the survival of rectal cancer patients with lymph node involvement.