• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3395-3402
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• 2015

Background: Preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy is a standard treatment for locally advanced colorectal cancer (CRC). However, CRC cells often develop chemoradiation resistance (CRR). Recent studies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processes and human diseases, as well as chemotherapy resistance. Since the roles of lncRNAs in 5-FU-based CRR in human CRC cells remain unknown, they were investigated in this study. Materials and Methods: A 5-FU-based concurrent CRR cell model was established using human CRC cell line HCT116. Microarray expression profiling of lncRNAs and mRNAs was undertaken in parental HCT116 and 5-FU-based CRR cell lines. Results: In total, 2,662 differentially expressed lncRNAs and 2,398 mRNAs were identified in 5-FU-based CRR HCT116 cells when compared with those in parental HCT116. Moreover, 6 lncRNAs and 6 mRNAs found to be differentially expressed were validated by quantitative real time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated involvement of many, such as Jak-STAT, PI3K-Akt and NF-kappa B signaling pathways. To better understand the molecular basis of 5-FU-based CRR in CRC cells, correlated expression networks were constructed based on 8 intergenic lncRNAs and their nearby coding genes. Conclusions: Changes in lncRNA expression are involved in 5-FU-based CRR in CRC cells. These findings may provide novel insight for the prognosis and prediction of response to therapy in CRC patients.

• Radiation Oncology Journal
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• v.15 no.2
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• pp.113-119
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• 1997

Purpose : Radical gastrectomy is main treatment of gastric cancer. But the result is not satisfactory with surgery alone. Most of pattern of failure remain locoregional recurrence. To improve 5 year survival postoperative chemotherapy with or without radiotherapy has been used. We analyzed patients with stage III and IV stomach cancer who had radical operation and received postoperative radiation therapy combined with or without chemotherapy retrospectively. Material and Method : From March 1985 to June 1993, 68 patients treated with curative resection and received postoperative adiuvant radiotherapy with 36Gy or more were evaluated. Median age was 60 years(range 28-66 yrs) . Patients were followed from 3 to 133 months with median follow up of 48 months. Thirty seven patients had non signet ring adenocarcinoma, 29 signet ring cell, 2 other cell. Patients with stage IIIA, IIIB, IV disease were 19, 25 and 24 respectively Chemotherapy was given to all patients except two. Results : Five-year overall survival and disease-free survival rate were 36.6% and 33.6%, respectively. Prognostic factor affecting survival were assessed. High ratio of jnvolved/dissected Iymph node, signet ring histology showed Poor Prognosis with statistical significance. Presence of residual tumor after surgery, stageIV. split course of radiation therapy, age, number of involved Iymph node, number of Iymph node dissection and grade of tumor affected survival without statistical significance, Type of chemotherapy did not affect survival. Recurrence was documented in 34 patients. High recurrence was seen in omentum and peritoneum with 23.5%, and remnant stomach, anastomosis site, A-loop and I-loop had also high recurrence with 13.2%. In field locoregional recurrence was 20.7% and total distant metastases were 39.7%. Total intraabdominal failure was 47.1% and extraabdominal failure was 13.2%. Treatment toxicity was considered to be acceptable. 22.1% of patients had grade 3 and only 1 patient had grade 4 leukopenia. Six Patients(8.8%) had weigh loss more than 10%. Conclusion : Treatment toxicity was acceptable with combined treatment with chemotherapy and radiotherapy. Locoregional recurrence was relatively low compared to distant failure with addition of irradiation. Peritoneal and omental seeding was high Five-rear surival was increased with combined modality. Radiation may eradicate minimal residual disease and improve survival, To evaluate role of radiation Prospective randomized study employing chemotherapy alone and chemotherapy plus radiation is necessary. Futhermore to reduce intraabdominal failure, role of intraabdominal chemotherapy in addition to combined chemotherapy plus radiation has to be explored.

• Radiation Oncology Journal
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• v.5 no.2
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• pp.97-104
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• 1987

From January 1970 through December 1984, 15 patients with sinonasal Non-Hodgkin's lymphoma combined to the head and neck were treated by external irradiation.13 patients were stage It and 2 were stage IIE by Ann Arbor Classification. However, when using TNM system, 7 were locally advanced T3, T4 lesions. All patients had follow up from 3.7 to 16 years with the median follow-up of 8.5 years. The overall actuarial 5-year survival rates were $25\%,\;28\%$ for IE and $0\%$ for IIE. Total tumor dose varied from 40 to 68 Gy. $100\%$ complete response with a total tumor dose of more than 55 Gy and $73\%$ complete response with less than 55Gy. When the disease was staged using the TNM (AJC) system, the five-year disease free survival for T1 and T2 patients was $50\%$ as compared with $14\%$ for T3 and T4. Failure rate by stage was $33\%(2/6)$ for T1 and T2, $86\%(6/7)$ for T3 and T4, and $100\%$(2/2) for IIE. The results suggest that 1. Higher CR could be obtained with a total tuner dose of more than 55 Gy. 2. Use of TNM staging system is as important as Ann arbor in management of sinonasal NHL. 3. The addition of combination chemotherapy should be considered for T3, T4 and IIE the sinonasal Non-Hodgkin's lymphoma although the disease is limited to head and neck.

• Radiation Oncology Journal
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• v.13 no.4
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• pp.311-319
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• 1995

Purpose : To evaluate the survival and prognostic factors in patients with stage III non-small cell lung cancer treated with curative radiotherapy alone or combined with chemotherapy Materials and Methods : A retrospective analysis was undertaken of 35 patients who had locally advanced non-small-cell lung cancer and treated with curative radiotherapy in Department of Therapeutic Radiology, Kangdong Sacred Heart Hospital, from January 1991 through December 1993. According to AJCC staging, 15 patients were stage IIIA, and 20 were stage IIIB. Radiotherapy was delivered with 1 8-2 Gy per fraction/day. 5 days per week using 6 MV X-ray, to a total dose ranging from 48.8 Gy to 66.6 Gy (median, 61.2 Gy) in 4 to 9 weeks. Ten patients received neoadjuvant or concurrent chemotherapy with FIP (5-FU, ifosfamide, and cisplatin) or FP (5-FU and cisplatin) Results : For all Patients, median survival was 6 months. 1-year and 2-year survival rates were 23.3% and 6.7%, respectively The median survival was 8 months in stage IIIA and 5.5 months in stage IIIB. In patients treated with radiation therapy alone, median survival was 5 months and 1-year survival rate was 9%. In patients who received chemotherapy, median survival was 11 months and 1-year survival rate was 60%. The difference of survival between these two groups was statistically significant (p=0.03). Total radiation dose, degree of response, and Post-treatment ECOG score were also significantly associated with survival. But it was not affected by age, sex, pretreatment ECOG score, presence or absence of weight loss, tumor location. pathologic type, N stage, and degree of response to treatment. Conclusion : Conventional radiotherapy alone is unlikely to achieve long term survival in patients with stage III NSCLC. Radiotherapy with altered fractionation schedule or multimodality treatment combined with surgery and/or chemotherapy should be considered if feasible.

• Radiation Oncology Journal
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• v.26 no.4
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• pp.213-221
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• 2008

Purpose: The objective of this retrospective study was to identify predictive factors for the complete pathologic response and tumor downstaging after preoperative concurrent chemoradiotherapy for locally advanced rectal cancer. Materials and Methods: Between the years 2000 and 2008, 39 patients with newly diagnosed rectal cancer without prior evidence of distant metastasis received preoperative concurrent chemoradiotherapy followed by surgery. The median radiation dose was 50.4 Gy (range, $45{\sim}59.4\;Gy$)). Thirty-eight patients received concurrent infusional 5-fluorouracil and leucovorin, while one patient received oral capecitabine twice daily during radiotherapy. Results: A complete pathologic response (CR) was demonstrated in 12 of 39 patients (31%), while T-downstaging was observed in 24 of 39 patients (63%). N-downstaging was observed in 18 of 28 patients (64%), with a positive node in the CT scan or ultrasound. Two patients with clinical negative nodes were observed in surgical specimens. The results from a univariate analysis indicated that the tumor circumferential extent was less than 50% (p=0.031). Moreover, the length of the tumor was less than 5 cm (p=0.004), while the post-treatment carcinoembryonic antigen (CEA) levels were less than or equal to 3.0 ng/mL (p=0.015) and were significantly associated with high pathologic CR rates. The univariate analysis also indicated that the adenocarcinoma (p=0.045) and radiation dose greater than or equal to 50 Gy (p=0.021) were significantly associated with high T-downstaging, while a radiotherapy duration of less than or equal to 42 days (p=0.018) was significantly associated with N-downstaging. The results from the multivariate analysis indicated that the lesser circumferential extent of the tumor (hazard ratio [HR] 0.150; p=0.028) and shorter tumor length (HR, 0.084; p=0.005) independently predicted a higher pathologic CR. The multivariate analysis also indicated that a higher radiation dose was significantly associated with higher T-downstaging (HR, 0.115; p=0.025), while the shorter duration of radiotherapy was significantly associated with higher N-downstaging (HR, 0.028; p=0.010). Conclusion: The circumferential extent of the tumor and its length was a predictor for the pathologic CR, while radiation dose and duration of radiotherapy were predictors for tumor downstaging. Hence, these factors may be used to predict outcomes for patients and to develop further treatment guidelines for high-risk patients.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.303-310
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• 1998

Purpose : To evaluate the results of the treatment of locally advanced but resectable rectal cancers and to analyze prognostic factors. especially with the emphasis on the treatment time factor. Materials and Methods : There were 71 patients with rectal cancer who had been treated by curative surgical procedure and postoperative radiotherapy from August 1989 to December 1993. The minimum follow up period was 24 months and the median follow-up was 35 months Radiation therapy had been given by 6 MV linear accelerator by parallel opposing or four-box portals. Whole pelvis was treated up to 5040 cGy in most cases. Systemic chemotherapy had been given in 94$\%$ of the patients, mostly with 5-FU/ACNU regimen. Assessment for the overall and disease-free survival rates were done by life-table method and prognostic factors by Log-Rank tests. Results : Five-year overall survival, disease-free survival were 58.8$\%$ and 57$\%$, respectively. Two-year local control rate was 76.6$\%$. Stage according to Modified Astler-Coller (MAC) system, over 4 positive lymph nodes, over 6weeks interval between definitive surgery and adjuvant radiotherapy and over 7 days of interruption during radiotherapy period were statistically significant, or borderline significant prognostic factors. Conclusion : The treatment results of patients with rectal cancers are comparable to those of other large institutes. The treatment results for the patients with bowel wall penetration and/or positive regional lymph nodes were still discouraging for their high local recurrence rate for the patients with MAC 'c' stage diseases and high distant metastases rate even for the patients with node-negative diseases. Maybe more effective regimen of chemotherapy would be needed with proper route and schedule. To maximize postoperative adjuvant treatment. radiotherapy should be started at least within 6 weeks after surgery and preferably as soon as wound healing is completed. Interruption of treatment during radiotherapy course affects disease-free survival badly, especially if exceeds 7 days. So, the total treatment period trout definitive surgery to the completion of radiotherapy should be kept as minimal as possiable.

• Radiation Oncology Journal
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• v.7 no.2
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• pp.247-257
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• 1989

Thirty patients with nonresectable hepatocellular carcinoma (HCC) due to either locally advanced lesion or association with liver cirrhosis, treated with combined radiotherapy and hyperthermia between April 1988 and July 1988, at Dept. of Radiation Oncology, Yonsei university College of medicine, were analysed. External radiotherapy of a total dose of 3060cGy/3.5 wks was given. Hyperthermia was given twice a week with a total of 6 treatment sessions using 8MHz radiofrequency capacitive type heating device, i.e., Thermotron RF-8 and Cancermia. In all cases hyperthermia was given within 30 minutes after radiotherapy for 30~60min. Temperature was measured by inserting thermocouple into the tumor mass under the ultrasonographic guidance only for those who had not bleeding tendency. As a result, partial response (PR) was achieved in 12 patients (40%), and symptomatic improvement was observed in 22 patients (78.6%) among 28 patients who had suffered from abdominal pain. The most significant factor affecting the tumor response rate was the type of tumor (single massive: 10/14, 71.4%; diffuse infiltrative: 2/10, 20%; multinodular:0/6, 0%; p<0.005). There were not any significant side effects relating to combined treatment. The overall 1 year survival rate was 34%, with 50% in the PR group and 22% in the no response group (NR), respectively. Median survival was 6.5 months and longer for those of PR than of NR (11 mos. vs 5, p<0.05). In conclusion, combined radiotherapy and hyperthermia appeared to be effective in local control and symptomatic palliation of HCC. Further study including a larger number of the patients to confirm its effect in survival and detrimental side effect should be urged.

• Radiation Oncology Journal
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• v.9 no.2
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• pp.311-317
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• 1991

Ten patients with deep muscle-invading bladder carcinoma (clinical stages T3a to T4b) who were not candidates for cystectomy were treated with combined modality treatment with transurethral resection, cisplatin chemotherapy and pelvic irradiation from 1989 through 1990, and were analyzed retrospectively. All patients were not candidates for cystectomy because the tumors were judged unresectable or they were not fit for a radical cystectomy. Of the patients 5 had clinical stage T3a, 3 stage T3b and 2 stage T4b disease. The minimum follow-up was 16 months. The complete response rate is 60$\%$ for all patients. The complete responses were achieved in 4 of 5(80$\%$) with stage cT3a, in 2 of 3(67$\%$)with stage cT3b and in none of 2(0$\%$) with stage cT4b. The partial responses were achieved in 2, so an overall response rate was 80$\%$. All six patients with grade I or II transitional cell carcinoma showed complete responses. Four patients with higher grade tumors showed partial responses in 2 and no response in 2, and all died of their bladder cancer. Six patients who showed complete responses after treatment are alive and only one of them showed a local recurrence 10 months after treatment. Distant metastases developed in 3 patients: lungs in 2(cT4b) of those who were never locally free of disease and spine in 1 patient (cT3b) among those with a partial response. Two patients died of metastases to lungs. During the follow-up diarrhea occurred in one which was improved after conservative treatment. On the basis of this analysis it is suggested that combined modality treatment seems to be a tolerable regimen and can be offered with a relatively high probability of success and conservation of bladder function in those with less advanced tumors by clinical stage and low grade.

• Radiation Oncology Journal
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• v.19 no.3
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• pp.224-229
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• 2001

Purpose : The aim of this study is to analyze the treatment failure patterns and the risk factors for locoregional or distant failure of uterine cervical carcinoma treated with radiation therapy. Materials and methods . A retrospective analysis was undertaken of 154 patients treated with curative radiation therapy in Gyeongsang National University Hospital from April 1989 through December 1997. According to FIGO classification, 12 patients were stage IB, 24 were IIA, 98 were IIB, 1 were IIIA, 17 were IIIB, 2 were IVA. Results : Overall treatment failure rate was $42.1\%$ (65/154), and that of complete responder was $31.5\%$ (41/130). Among 65 failures, 25 failed locoregionally, another 25 failed distantly, and 15 failed locoregionally and distantly. Multivariate analysis confirmed tumor size (>4 cm) as risk factor for locoregional failure, and tumor size (>4 cm), pelvic lymph node involvement as risk factors for distant failure. Conclusion : On the basis of results of our study and recent published data of prospective randomized study for locally advanced uterine cervical carcinoma, we concluded that uterine cervical carcinoma with size more than 4 cm or pelvic lymph node involvement should be treated with concurrent chemoradiation.

• Radiation Oncology Journal
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• v.16 no.4
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• pp.447-454
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• 1998

Purpose : This study evaluated the survival, local control, prognostic factor, and failure pattern of patients with esophageal cancer treated with operation and adjuvant radiation therapy to use as fundermental data of postoperative radiation therapy. Materials and Methods : A retrospective analysis was undertaken of 82 patients who had locally advanced esophageal cancer treated with operation and adjuvant radiation therapy from January 1988 to December 1995. According to AJCC staging, stage IIA were in 26 patients, stage IIB in 4 patients, and stage III in 52 patients. Squamous cell carcinoma were in 77 patients, adenosquamous carcinoma in 3 patients, and adenocarcinoma in 2 patients. The patients received radiation therapy ranging from 41.0 Gy to 64.8 Gy. Five patients received neoadjuvant chemotherapy. Results : Two-year survival and local control rates for all patients were 36.8$\%$ and 30.4$\%$ respectively. And they were 9.3$\%$ and 26.3$\%$ respectively at 5 years. According to stages, 2-year survival rates were 50.2$\%$ in IIA, 0$\%$ in IIB and 23.3$\%$ in III (p=0.004). Two-year local control rates were 49.2 $\%$ in IIA, 66.6$\%$ in IIB and 24.7$\%$ in III (p=0.01). Sixty patients developed recurrence, which were 3 tumor margin, 23 lymph node recurrence, 4 tumor margin and lymph node, 1 tumor margin and distant metastasis, 9 lymph node and distant metastasis, 17 distant metastasis and 3 unknown metastatic site. Prognostic factors affecting survival were smoking (p=0.02), T-staging (p=0.0092), N-staging (p=0.0045). Prognostic factors affecting local control were T-staging (p=0.019), N-staging (p=0.047). Conclusion : In spite of post-operative radiation therapy, predominant failure pattern was local failure. Especially regional lymph node failure was major cause of local failure. So strategy of aggresive adjuvant radiation therapy to regional lymph node area in post operative treatment should be proposed.