• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7315-7319
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• 2015

Objectives: The study analyzed and compared the long term outcome in locally advanced rectal cancer treated with preoperative and postoperative concurrent chemoradiation (CCRT). Materials and Methods: A retrospective review of 105 patients with stage T3-T4 or regional lymph node positive adenocarcinoma of rectum treated with preoperative or postoperative CCRT at Ramathibodi Hospital during 2005 to 2010 was performed. The results of treatment were reported with 5-year overall survival (OS), 5-year locoregional recurrence free survival (LRFS), and toxicity according to preoperative versus postoperative concurrent chemoradiation (CCRT) groups. Results: Among 105 patients, 34 (32%) were treated with preoperative CCRT and 71 (68%) with postoperative CCRT. At the median follow-up time of 50.5 months (range 2-114 months), five-year OS and LRFS of all patients were 87% and 91.6%, respectively. The study found no difference in 5-year OS (81.7% vs 89.2 %) or LRFS (83.4% vs 95.1%) between preoperative versus postoperative CCRT. Seven cases of loco-regional recurrence were diagnosed, 4 (11.8%) after preoperative CCRT and 3 (4.2%) after postoperative CCRT. The recurrent sites were anastomosis in all patients. There was no significant factor associated with outcome after univariate and multivariate testing. Grade 3 or 4 acute and late complications were low in both preoperative and postoperative CCRT groups. Conclusions: Locally advanced rectum cancer patients experience good results with surgery and adjuvant concurrent chemoradiation.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3769-3772
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• 2013

Background: To investigate the impact of the lymph node ratio (LNR) on the prognosis of patients with locally advanced rectal cancer undergoing pre-operative chemoradiation. Methods: Clinicopathologic and follow up data of 128 patients with stage III rectal cancer who underwent curative resection from 1996 to 2007 were reviewed. The patients were divided into two groups according to the lymph node ratio: LNR ${\leq}$ 0.2 (n=28), and >0.2 (n=100). Kaplan-Meier and the Cox proportional hazard regression models were used to evaluate the prognostic effects according to LNR. Results: Median numbers of lymph nodes examined and lymph nodes involved by tumour were 10.3 (range 2-28) and 5.8 (range 1-25), respectively, and the median LNR was 0.5 (range, 0-1.6). The 5-year survival rate significantly differed by LNR (${\leq}$ 0.2, 69%; >0.2, 19%; Log-rank p value < 0.001). LNR was also a significant prognostic factor of survival adjusted for age, sex, post-operative chemotherapy, total number of examined lymph nodes, metastasis and local recurrence (${\leq}$ 0.2, HR=1; >0.2, HR=4.8, 95%CI=2.1-11.1) and a significant predictor of local recurrence and distant metastasis during follow-up independently of total number of examined lymph node. Conclusions: Total number of examined lymph nodes and LNR were significant prognostic factors for survival in patients with stage III rectal cancer undergoing pre-operative chemoradiotherapy.

• Radiation Oncology Journal
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• v.35 no.2
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• pp.129-136
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• 2017

Purpose: The concentration of capecitabine peaks at 1-2 hours after administration. We therefore assumed that proper timing of capecitabine administration and radiotherapy would maximize radiosensitization and influence survival among patients with locally advanced rectal cancer. Materials and Methods: We retrospectively reviewed 223 patients with locally advanced rectal cancer who underwent preoperative chemoradiation, followed by surgery from January 2002 to May 2006. All patients underwent pelvic radiotherapy (50 Gy/25 fractions) and received capecitabine twice daily at 12-hour intervals ($1,650mg/m^2/day$). Patients were divided into two groups according to the time interval between capecitabine intake and radiotherapy. Patients who took capecitabine 1 hour before radiotherapy were classified as Group A (n = 109); all others were classified as Group B (n = 114). Results: The median follow-up period was 72 months (range, 7 to 149 months). Although Group A had a significantly higher rate of good responses (44% vs. 25%; p = 0.005), the 5-year local recurrence-free survival rates of 93% in Group A and 97% in Group B did not differ significantly (p = 0.519). The 5-year disease-free survival and overall survival rates were also comparable between the groups. Conclusions: Despite the better pathological response in Group A, the time interval between capecitabine and radiotherapy administration did not have a significant effect on survivals. Further evaluations are needed to clarify the interaction of these treatment modalities.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.89-93
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• 2016

Background: Limited data are available regarding the impact of time duration between chemoradiation (CRT) and surgery on pathological complete response (PCR). A PCR translates into better overall and disease free survival. The objective of this study was to determine effect of time duration on outcome after preoperative CRT in rectal cancer. Materials and Methods: A retrospective review of patients undergoing operations for rectal adenocarcinoma between January 2005 and December 2010 was performed. Patients were divided in two groups: Group 1 underwent surgery in ${\leq}8weeks$ post neoadjuvant CRT and Group 2 after 8 weeks. Patient characteristics, surgical procedure, histopathological details and number of loco-regional and distant failures were compared. Expected 5 year overall survival and disease free survival was calculated using Kaplan Meier curves and significance was determined using the log rank test. Results: There were 66 patients in group 1 and 93 in group 2. No significant difference in PCR was observed between the two. However, estimated 5 year DFS was significantly higher in Group 1 (66.7%) as compared to Group 2 (53.8%) (P=0.04). Estimated overall 5 year overall survival was not significantly different at 68.2% versus 54.3% (P= 0.09). Conclusions: Delaying surgery more than 8 weeks after preoperative CRT does not impact for PCR in rectal cancer.

• Radiation Oncology Journal
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• v.13 no.3
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• pp.233-241
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• 1995

Purpose : To analyse clinical outcome and prognostic factors according to treatment modality, this paper report our experience of retrospective study of patients with esophageal cancer Materials and Methods : One hundred and ten patients with primary esophageal cancer who were treated in Presbyterian Medical Center from May 1985 to December 1992. We analysed these patients retrospectively with median follow up time of 28 months, one hundred and four patients($95{\%}$) were followed up from 15 to 69 months. In methods, twenty-eight patients were treated with median radiation dose irradiated 54.3Gy only. Fifty-six patients were treated with combined chemoradiotherapy. Sixteen cases of these patients were treated with concurrent chemoradiation and the other patients(forty cases) were treated sequential chemoradiotherapy. In concurrent chemoradiotherapy group, patients received 5-FU continuous IV infusion for 4 days. Cisplatin IV bolus. and concurrent esophageal irradiation to 30 Gy. After that patients received 5-FU continuous IV, Cisplatin bolus injection and Mitomycin-C bolus IV, Bleomycin continuous IV, and irradiation to 20 Gy. In sequential chemoradiotherapy group, the chemotherapy consisted of 5-FU 1,000mg/$m^2$ administered as a continuous 24 hour intravenous infusion during five days and Cisplatin 80-100mg/$m^2$ bolus injected, or Bleomycin, Vinblastine, Cisplatin, Methotrexate were used of 1 or 2 cycles. After preoperative concurrentm chemoradiation twenty-six patients underwent radical esophagectomy. Results : Ninety-three patients could be examined for response assessment, By treatment modality, response rates were $85.1{\%}$ for radiation alone group and $86.3{\%}$ for combined chemoradiation group. But in operation group, after one cycle of concurrent chemoradiation treatment, response rate was $61.9{\%}$. The pathologic complete response were $15.4{\%}$ in operation group. Overall median survival was II months and actuarial 5-year survival rate was $8{\%}$. The median survival interval was 6 months for radiation alone group, 11 months for combined chemoradiation group and 19 months for operation group. And also median survival was 19 months for complete responder group that 8 months for noncomplete responder group. In univariative analysis, statistically significant prognostic factors were tumor size, clinical stage, tumor response, and operation. In multivariative analysis, significantly better survival was associated with clinical stage, tumor response, radiation dose, and operation. Conclusion : Compared with radiotherapy alone, combined multimodality may improve the median survival in patients with localized carcinoma of the esophagus and toxicity is acceptable.

• Radiation Oncology Journal
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• v.26 no.1
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• pp.56-64
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• 2008

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.

• Journal of Gastric Cancer
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• v.20 no.3
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• pp.313-327
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• 2020

Purpose: Nodal downstaging after preoperative therapy for gastric cancer has been shown to impart excellent prognosis, but this has not been validated in a national cohort. The role of neoadjuvant chemoradiation (NACR) in nodal downstaging remains unclear when compared with that of neoadjuvant chemotherapy alone (NAC). Furthermore, it is unknown whether the prognostic implications of nodal downstaging differ by preoperative regimen. Materials and Methods: Using the National Cancer Database, overall survival (OS) duration was compared among natural N0 (cN0/ypN0), downstaged N0 (cN+/ypN0), and nodepositive (ypN+) gastric cancer patients treated with NACR or NAC. Factors associated with nodal downstaging were examined in a propensity score-matched cohort of cN+ patients, matched 1:1 by receipt of NACR or NAC. Results: Of 7,426 patients (natural N0 [n=1,858, 25.4%], downstaged N0 [n=1,813, 24.4%], node-positive [n=3,755, 50.4%]), 58.2% received NACR, and 41.9% received NAC. The median OS durations of downstaged N0 (5.1 years) and natural N0 (5.6 years) patients were similar to one another and longer than that of node-positive patients (2.1 years) (P<0.001). In the matched cohort of cN+ patients, more recent diagnosis (2010-2015 vs. 2004-2009) (odds ratio [OR], 2.57; P<0.001) and NACR (OR, 2.02; P<0.001) were independently associated with nodal downstaging. The 5-year OS rate of downstaged N0 patients was significantly lower after NACR (46.4%) than after NAC (57.7%) (P=0.003). Conclusions: Downstaged N0 patients have the same prognosis as natural N0 patients. Nodal downstaging occurred more frequently after NACR; however, the survival benefit of nodal downstaging after NACR may be less than that when such is achieved by NAC.

• Radiation Oncology Journal
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• v.29 no.1
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• pp.11-19
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• 2011

Purpose: To evaluate the pathological and clinical effects of preoperative chemoradiation (CCRT) in cases of locally advanced rectal cancer and to determine the predictive factors for tumor downstaging. Materials and Methods: From March 2004 to August 2008, 33 patients with locally advanced rectal cancer were treated with preoperative CCRT. Twenty-eight patients (84.8%) were treated using a concomitant boost technique while five (15.2%) patients were treated using a cone down boost technique. All patients received 50.4 Gy of irradiation and concurrent chemotherapy with 5-fluorouracil. The median follow-up duration was 24.2 months (range, 9.8 to 64.7 months). Results: Thirty-one (93.9%) patients underwent surgery. Twenty-four patients (72.7%) underwent anal sphincter-preserving surgery. The 3-year disease free survival (DFS) and overall survival rates were 63.4% and 78.8%, respectively. Post-operative factors were more important for DFS. Pathologic N stage, margin status, and pathologic differentiation were significant prognostic factors (p=0.001, 0.029, 0.030). Tumor size and lymphovascular invasion were also associated with marginal significance (p=0.081, 0.073). However, only pre-treatment T stage was a significant pre-operative factor (p=0.018). The complete pathological response rate was 9.1 %. T-downstaging was observed in ten (30.3%) patients, whereas N-downstaging was found in 24 (72.7%) patients. Pre-treatment T stage and the interval between CCRT and operation were the predictive factors for downstaging in a univariate analysis (p=0.029, 0.027). Pre-treatment carcinoembryogenic antigen was also associated with marginal significance (p=0.068). Conclusion: The survival of rectal cancer patients can be better determined based on post-operative findings. Therefore, pre-operative CCRT for downstaging of the tumor seems to be important. Pre-treatment T stage and the interval between CCRT and operation can be used to predict downstaging.

• Radiation Oncology Journal
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• v.34 no.2
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• pp.96-105
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• 2016

Purpose: The standard radiation dose for patients with locally rectal cancer treated with preoperative chemoradiotherapy is 45-50 Gy in 25-28 fractions. We aimed to assess whether a difference exists within this dose fractionation range. Materials and Methods: A retrospective analysis was performed to compare three dose fractionation schedules. Patients received 50 Gy in 25 fractions (group A), 50.4 Gy in 28 fractions (group B), or 45 Gy in 25 fractions (group C) to the whole pelvis, as well as concurrent 5-fluorouracil. Radical resection was scheduled for 8 weeks after concurrent chemoradiotherapy. Results: Between September 2010 and August 2013, 175 patients were treated with preoperative chemoradiotherapy at our institution. Among those patients, 154 were eligible for analysis (55, 50, and 49 patients in groups A, B, and C, respectively). After the median follow-up period of 29 months (range, 5 to 48 months), no differences were found between the 3 groups regarding pathologic complete remission rate, tumor regression grade, treatment-related toxicity, 2-year locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, or overall survival. The circumferential resection margin width was a prognostic factor for 2-year locoregional recurrence-free survival, whereas ypN category was associated with distant metastasis-free survival, disease-free survival, and overall survival. High tumor regression grading score was correlated with 2-year distant metastasis-free survival and disease-free survival in univariate analysis. Conclusion: Three different radiation dose fractionation schedules, within the dose range recommended by the National Comprehensive Cancer Network, had no impact on pathologic tumor regression and early clinical outcome for locally advanced rectal cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4857-4860
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• 2014

Background: Colorectal cancer is common in Iran. However our knowledge about survival of rectal cancer in our province is low. The aim of this study is to evaluate this question. Materials and Methods: Patients with documented pathology of adenocarcinoma of the rectum and rectosigmoid junction referred to our center from September 2004 to September 2012 were enrolled in this study. Metastatic and recurrent patients were excluded. A questionnaire including clinicopathologic parameters, quality and sequence of treatment modalities was filled in for each patient. Patients treated with a combination of surgery, chemotherapy and radiation therapy were divided into standard and non-standard treatment groups, according to the sequence of treatment. Results: One hundred and nineteen patients were evaluated. Mean age was 60.8 year. The median overall survival was 62 months and five year survival was 55%. TNM staging system was not possible due to (Nx) in 21 (17.6%) patients. The others were in stage I, 20 patients (16.8%), II, 35 (29%.5) and III, 43(36.1%). According to our definition only 25 patients (21%) had been treated with standard treatment and 79% had not received it. A five year survival in patients with standard treatment was 85% and in the non-standard group it was 52%.Age, sex, stage and grade of tumor did not show any significant relation to survival. Conclusions: Our study showed a five year survival of rectal cancer in our patients was about 10% lower than the rate which is reported for developed countries. Preoperative concurrent chemoradiation significantly improved local control and even overall survival.