• 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.

• 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.

• Korean Journal of Radiology
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• v.25 no.4
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• pp.351-362
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• 2024

Objective: To measure inter-reader agreement and identify associated factors in interpreting complete response (CR) on magnetic resonance imaging (MRI) following chemoradiotherapy (CRT) for rectal cancer. Materials and Methods: This retrospective study involved 10 readers from seven hospitals with experience of 80-10210 cases, and 149 patients who underwent surgery after CRT for rectal cancer. Using MRI-based tumor regression grading (mrTRG) and methods employed in daily practice, the readers independently assessed mrTRG, CR on T2-weighted images (T2WI) denoted as mrCR_T2W, and CR on all images including diffusion-weighted images (DWI) denoted as mrCR_overall. The readers described their interpretation patterns and how they utilized DWI. Inter-reader agreement was measured using multi-rater kappa, and associated factors were analyzed using multivariable regression. Correlation between sensitivity and specificity of each reader was analyzed using Spearman coefficient. Results: The mrCR_T2W and mrCR_overall rates varied widely among the readers, ranging 18.8%-40.3% and 18.1%-34.9%, respectively. Nine readers used DWI as a supplement sequence, which modified interpretations on T2WI in 2.7% of cases (36/1341 [149 patients × 9 readers]) and mostly (33/36) changed mrCR_T2W to non-mrCR_overall. The kappa values for mrTRG, mrCR_T2W, and mrCR_overall were 0.56 (95% confidence interval: 0.49, 0.62), 0.55 (0.52, 0.57), and 0.54 (0.51, 0.57), respectively. No use of rectal gel, larger initial tumor size, and higher initial cT stage exhibited significant association with a higher interreader agreement for assessing mrCR_overall (P ≤ 0.042). Strong negative correlations were observed between the sensitivity and specificity of individual readers (coefficient, -0.718 to -0.963; P ≤ 0.019). Conclusion: Inter-reader agreement was moderate for assessing CR on post-CRT MRI. Readers' varying standards on MRI interpretation (i.e., threshold effect), along with the use of rectal gel, initial tumor size, and initial cT stage, were significant factors associated with inter-reader agreement.

• Journal of Korean Physical Therapy Science
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• v.11 no.3
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• pp.5-13
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• 2004

The use of therapeutic ultrasound(US) in humans with malignant neoplasms has been contra-indicated in physical therapy practice. Some studies have shown the results after application of US inhibited of tumor growth but some studies have shown the results facilitated of tumor growth in mouse. The purpose of this study were to determine the effects of US on rectal sarcoma(CT-26) in mouse and to determine the histological change of tumor. Thirty-five female BALB/C mouse, age 6 to 8 weeks received subcutaneous injection of 0.1 105 tumor cells. When tumors grew to 5 mm in diameters, the mouse were randomly assigned to control group(n=7) and high powered continuous US group(n=7) and low powered continuous US group(n=7) and high powered pulsed US group(n=7) and low powered pulsed US group(n=7). The experimental group (four groups) received 10 treatments over a 10-day period of 3 MHz ultrasound. Tumor dimension were measured on days 1(start of treatment), 5(midtreatment), and 10(end of treatment, preexcision and postexcision). Tumors were weighed after excision and the mouse were observated histological change of tumor. All tumors grew larger over time. Mean tumor weights(in grams) and volumes(in cubic millimeters) were 2.063 g and $2729.313\;mm^3$ for the high powered continuous US group 1.881 g and $2428.002\;mm^3$ for the low powered continuous US group 1.730 g and $2381.002\;mm^3$ for the high powered pulsed US 1.673 g and $2289.562\;mm^3$ for the low powered pulsed US group 1.670 g and $2297.333\;mm^3$ for the control group. Ultrasound increased the weight and volume of subcutaneous tumor in mouse. We urge caution in the use of ultrasound in the areas of tumors.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.4
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• pp.375-381
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• 2023

Numerous studies have revealed the importance of tumor-derived exosomes in rectal cancer (RC). This study aims to explore the influence of tumor-derived exosomal integrin beta-1 (ITGB1) on lung fibroblasts in RC along with underlying mechanisms. Exosome morphology was observed using a transmission electron microscope. Protein levels of CD63, CD9, ITGB1, p-p65 and p65 were detected using Western blot. To determine ITGB1's mRNA expression, quantitative real-time polymerase chain reaction was used. Moreover, levels of interleukin (IL)-8, IL-1β, and IL-6 in cell culture supernatant were measured via commercial ELISA kits. ITGB1 expression was increased in exosomes from RC cells. The ratio of p-p65/p65 as well as levels of interleukins in lung fibroblasts was raised by exosomes derived from RC cells, while was reduced after down-regulation of exosomal ITGB1. The increased ratio of p-p65/p65 as well as levels of pro-inflammatory cytokines caused by exosomes from RC cells was reversed by the addition of nuclear factor kappa B (NF-κB) inhibitor. We concluded that the knockdown of RC cells-derived exosomal ITGB1 repressed activation of lung fibroblasts and the NF-κB pathway in vitro.

• Radiation Oncology Journal
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• v.35 no.3
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• pp.217-226
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• 2017

Purpose: Hematotoxicity following anti-cancer treatment is known to be related to treatment efficacy in several malignancies. The purpose of this study was to examine the hematologic parameters related to the tumor response and survival in patients treated with curative surgery following preoperative chemoradiotherapy (CRT) for rectal cancer. Materials and Methods: Four hundred eighteen patients with rectal cancer who underwent preoperative CRT and curative surgery were analyzed, retrospectively. The main clinical factors and blood cell counts before and after CRT were investigated with respect to their relationships with tumor downstaging and patient survival. Results: The post-CRT leukocyte count was significantly different between the tumor downstaging group and the non-downstaging group (median, 4740/uL vs. 5130/uL; p = 0.013). Multivariate analysis showed that histological grade, circumferential extent, and post-CRT leukocyte count were related to tumor downstaging. In addition, histological grade, post-CRT leukocyte count, and tumor downstaging were related to disease-free survival. The 5-year disease-free survival and overall survival in patients with post-CRT leukocyte count ${\leq}3730/uL$, which is the cut-off value derived from the receiver operation characteristic (ROC) curve analysis, were significantly higher than those with higher counts (88.0% vs. 71.6%, p = 0.001; 94.4% vs. 84.1%, p = 0.024). Conclusion: Post-CRT leukocyte count of ${\leq}3730/uL$ could be regarded as a good prognostic factor for tumor response and survival in rectal cancer patients treated with preoperative CRT.

• Radiation Oncology Journal
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• v.30 no.4
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• pp.205-212
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• 2012

Purpose: To evaluate the effect of pelvic radiotherapy (RT) in patients with stage IV rectal cancer treated with resection of primary tumor with or without metastasectomy. Materials and Methods: Medical records of 112 patients with stage IV rectal cancer treated with resection of primary tumor between 1990 and 2011 were retrospectively reviewed. Fifty-nine patients received synchronous or staged metastasectomy whereas fifty-three patients did not. Twenty-six patients received pelvic radiotherapy. Results: Median overall survival (OS), locoregional recurrence-free survival (LRFS), and progression-free survival (PFS) of all patients was 27, 70, and 11 months, respectively. Pathologic T (pT), N (pN) classification and complete metastasectomy were statistically significant factors in OS (p = 0.040, 0.020, and 0.002, respectively). RT did not improve OS or LRFS. There were no significant factors in LRFS. pT and pN classification were also significant prognostic factors in PFS (p = 0.010 and p = 0.033, respectively). In the subgroup analysis, RT improved LRFS in patients with pT4 disease (p = 0.026). The locoregional failure rate of the RT group and the non-RT group were 23.1% and 33.7%, showing no difference in the failure pattern of both groups (p = 0.260). Conclusion: Postoperative pelvic RT did not improve LRFS of all metastatic rectal cancer patients; however, it can be recommended to patients with pT4 disease. A complete resection of metastatic masses should be performed if possible.

• Radiation Oncology Journal
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• v.31 no.4
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• pp.252-259
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• 2013

Purpose: To report the results of dosimetric comparison between intensity-modulated radiotherapy (IMRT) using Tomotherapy and four-box field conformal radiotherapy (CRT) for pelvic irradiation of locally advanced rectal cancer. Materials and Methods: Twelve patients with locally advanced rectal cancer who received a short course preoperative chemoradiotherapy (25 Gy in 5 fractions) on the pelvis using Tomotherapy, between July 2010 and December 2010, were selected. Using their simulation computed tomography scans, Tomotherapy and four-box field CRT plans with the same dose schedule were evaluated, and dosimetric parameters of the two plans were compared. For the comparison of target coverage, we analyzed the mean dose, $V_{nGy}$, $D_{min}$, $D_{max}$, radical dose homogeneity index (rDHI), and radiation conformity index (RCI). For the comparison of organs at risk (OAR), we analyzed the mean dose. Results: Tomotherapy showed a significantly higher mean target dose than four-box field CRT (p = 0.001). But, $V_{26.25Gy}$ and $V_{27.5Gy}$ were not significantly different between the two modalities. Tomotherapy showed higher $D_{max}$ and lower $D_{min}$. The Tomotherapy plan had a lower rDHI than four-box field CRT (p = 0.000). Tomotherapy showed better RCI than four-box field CRT (p = 0.007). For OAR, the mean irradiated dose was significantly lower in Tomotherapy than four-box field CRT. Conclusion: In locally advanced rectal cancer, Tomotherapy delivers a higher conformal radiation dose to the target and reduces the irradiated dose to OAR than four-box field CRT.

• Radiation Oncology Journal
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• v.37 no.2
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• pp.110-116
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• 2019

Purpose: This study aimed to identify prognostic factors for locoregional recurrence (LRR) in pT3N0 rectal cancer patients who were treated with surgery alone and had negative resection margin including circumferential resection margin (CRM) for optimal indication of adjuvant radiotherapy. Materials and Methods: We reviewed patients with pT3N0 rectal cancer who were treated via upfront surgery and had no other adjuvant treatment from January 2003 to December 2012. In total, 122 patients who had negative resection margin including negative CRM were included in the analysis. Results: The median follow-up period after surgery was 60 months (range, 3 to 161 months). During this time, 6 patients (4.9%) experienced LRR at the anastomotic site (4 patients), and regional lymphatic area (2 patients). The estimated 5-year rates of overall survival, recurrence-free survival, and LRR-free survival were 96.7%, 84.6%, and 94.0%, respectively. Multivariate analysis showed that level of tumor ≤5 cm was a significant prognostic factor for LRR-free survival (LRRFS) (p = 0.04; hazard ratio = 7.08; 95% confidence interval, 1.06-47.30). Patients with level of tumor ≤5 cm had an estimated 5-year LRRFS of 66.8%, which was much higher than 2.3% in patients with level of tumor >5 cm. There was no significant factor for recurrence-free survival or overall survival. Conclusion: In T3N0 rectal cancer, adjuvant chemoradiotherapy should be recommended in patients with level of tumor ≤5 cm for better local control. However, in patients with pT3N0 disease, negative resection margin, and level of tumor >5 cm, adjuvant chemoradiotherapy should be carefully suggested.

• Radiation Oncology Journal
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• v.34 no.3
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• pp.177-185
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• 2016

Purpose: To investigate whether preoperative chemoradiotherapy (PCRT) followed by local excision (LE) is feasible approach in clinical T2N0 rectal cancer patients. Materials and Methods: Patients who received PCRT and LE because of clinical T2 rectal cancer within 7 cm from anal verge between January 2006 and June 2014 were retrospectively analyzed. LE was performed in case of a good clinical response after PCRT. Patients' characteristics, treatment record, tumor recurrence, and treatment-related complications were reviewed at a median follow-up of 49 months. Results: All patients received transanal excision or transanal minimally invasive surgery. Of 34 patients, 19 patients (55.9%) presented pathologic complete response (pCR). The 3-year local recurrence-free survival and disease free-survival were 100.0% and 97.1%, respectively. There was no recurrence among the patients with pCR. Except for 1 case of grade 4 enterovesical fistula, all other late complications were mild and self-limiting. Conclusion: PCRT followed by an LE might be feasible as an alternative to total mesorectal excision in good responders with clinical T2N0 distal rectal cancer.