• Biomolecules & Therapeutics
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• v.22 no.1
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• pp.78-81
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• 2014

Irinotecan suppository was prepared using the moulding method with a homogeneous blend. A sensitive and specific fluorescence method was developed and validated for the determination of irinotecan in plasma using HPLC. The pharmacokinetics of intravenous administered and rectal administered in rabbits was investigated. Following a single intravenous dose of irinotecan (50 mg/kg), the plasma irinotecan concentration demonstrated a bi-exponential decay, with a rapid decline over 15 min. $C_{max}$, $t_{1/2}$, $AUC_{0-30h}$ and $AUC_{0-{\infty}}$ were $16.1{\pm}2.7g/ml$, $7.6{\pm}1.2h$, $71.3{\pm}8.8{\mu}g{\cdot}h/ml$ and $82.3{\pm}9.5{\mu}g{\cdot}h/ml$, respectively. Following rectal administration of 100 mg/kg irinotecan, the plasma irinotecan concentration reached a peak of $5.3{\pm}2.5{\mu}g/ml$ at 4 h. The $AUC_{0-30h}$ and $AUC_{0-{\infty}}$ were $32.2{\pm}6.2{\mu}g{\cdot}h/ml$ and $41.6{\pm}7.2{\mu}g{\cdot}h/ml$, respectively. It representing ~50.6% of the absolute bioavailability.

• Radiation Oncology Journal
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• v.36 no.4
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• pp.276-284
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• 2018

Purpose: Traditionally, three-dimensional conformal radiation therapy (3D-CRT) is used for neoadjuvant chemoradiation in locally advanced rectal cancer. Intensity-modulated radiation therapy (IMRT) was later developed for more conformal dose distribution, with the potential for reduced toxicity across many disease sites. We sought to use the National Cancer Database (NCDB) to examine trends and predictors for IMRT use in rectal cancer. Materials and Methods: We queried the NCDB from 2004 to 2015 for patients with rectal adenocarcinoma treated with neoadjuvant concurrent chemoradiation to standard doses followed by surgical resection. Odds ratios were used to determine predictors of IMRT use. Univariable and multivariable Cox regressions were used to determine potential predictors of overall survival (OS). Propensity matching was used to account for any indication bias. Results: Among 21,490 eligible patients, 3,131 were treated with IMRT. IMRT use increased from 1% in 2004 to 22% in 2014. Predictors for IMRT use included increased N stage, higher comorbidity score, more recent year, treatment at an academic facility, increased income, and higher educational level. On propensity-adjusted, multivariable analysis, male gender, increased distance to facility, higher comorbidity score, IMRT technique, government insurance, African-American race, and non-metro location were predictive of worse OS. Of note, the complete response rate at time of surgery was 28% with non-IMRT and 21% with IMRT. Conclusion: IMRT use has steadily increased in the treatment of rectal cancer, but still remains only a fraction of overall treatment technique, more often reserved for higher disease burden.

• Radiation Oncology Journal
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• v.23 no.3
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• pp.143-156
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• 2005

Background: The best dose-fractionation regimen of the definitive radiotherapy for cervix cancer remains to be clearly determined. It seems to be partially attributed to the complexity of the affecting factors and the lack of detailed information on external and intra-cavitary fractionation. To find optimal practice guidelines, our experiences of the combination of external beam radiotherapy (EBRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT) were reviewed with detailed information of the various treatment parameters obtained from a large cohort of women treated homogeneously at a single institute. Materials and Methods: The subjects were 743 cervical cancer patients (Stage IB 198, IIA 77, IIB 364, IIIA 7, IIIB 89 and IVA 8) treated by radiotherapy alone, between 1990 and 1996. A total external beam radiotherapy (EBRT) dose of $23.4\~59.4$ Gy (Median 45.0) was delivered to the whole pelvis. High-dose-rate intracavitary brachytherapy (HDR-IBT) was also peformed using various fractionation schemes. A Midline block (MLB) was initiated after the delivery of $14.4\~43.2$ Gy (Median 36.0) of EBRT in 495 patients, while In the other 248 patients EBRT could not be used due to slow tumor regression or the huge initial bulk of tumor. The point A, actual bladder & rectal doses were individually assessed in all patients. The biologically effective dose (BED) to the tumor ($\alpha/\beta$=10) and late-responding tissues ($\alpha/\beta$=3) for both EBRT and HDR-ICBT were calculated. The total BED values to point A, the actual bladder and rectal reference points were the summation of the EBRT and HDR-ICBT. In addition to all the details on dose-fractionation, the other factors (i.e. the overall treatment time, physicians preference) that can affect the schedule of the definitive radiotherapy were also thoroughly analyzed. The association between MD-BED $Gy_3$ and the risk of complication was assessed using serial multiple logistic regression models. The associations between R-BED $Gy_3$ and rectal complications and between V-BED $Gy_3$ and bladder complications were assessed using multiple logistic regression models after adjustment for age, stage, tumor size and treatment duration. Serial Coxs proportional hazard regression models were used to estimate the relative risks of recurrence due to MD-BED $Gy_{10}$, and the treatment duration. Results: The overall complication rate for RTOG Grades $1\~4$ toxicities was $33.1\%$. The 5-year actuarial pelvic control rate for ail 743 patients was $83\%$. The midline cumulative BED dose, which is the sum of external midline BED and HDR-ICBT point A BED, ranged from 62.0 to 121.9 $Gy_{10}$ (median 93.0) for tumors and from 93.6 to 187.3 $Gy_3$ (median 137.6) for late responding tissues. The median cumulative values of actual rectal (R-BED $Gy_3$) and bladder Point BED (V-BED $Gy_3$) were 118.7 $Gy_3$ (range $48.8\~265.2$) and 126.1 $Gy_3$ (range: $54.9\~267.5$), respectively. MD-BED $Gy_3$ showed a good correlation with rectal (p=0.003), but not with bladder complications (p=0.095). R-BED $Gy_3$ had a very strong association (p=<0.0001), and was more predictive of rectal complications than A-BED $Gy_3$. B-BED $Gy_3$ also showed significance in the prediction of bladder complications in a trend test (p=0.0298). No statistically significant dose-response relationship for pelvic control was observed. The Sandwich and Continuous techniques, which differ according to when the ICR was inserted during the EBRT and due to the physicians preference, showed no differences in the local control and complication rates; there were also no differences in the 3 vs. 5 Gy fraction size of HDR-ICBT. Conclusion: The main reasons optimal dose-fractionation guidelines are not easily established is due to the absence of a dose-response relationship for tumor control as a result of the high-dose gradient of HDR-ICBT, individual differences In tumor responses to radiation therapy and the complexity of affecting factors. Therefore, in our opinion, there is a necessity for individualized tailored therapy, along with general guidelines, in the definitive radiation treatment for cervix cancer. This study also demonstrated the strong predictive value of actual rectal and bladder reference dosing therefore, vaginal gauze packing might be very Important. To maintain the BED dose to less than the threshold resulting in complication, early midline shielding, the HDR-ICBT total dose and fractional dose reduction should be considered.

• Radiation Oncology Journal
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• v.13 no.3
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• pp.243-252
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• 1995

Purpose : Intraluminal high dose rate brachytherapy is an accepted treatment for the tumors of GI tract. However, there is only some limited clinical data for intraluminal high dose rate brachytherapy for the tumors of GI tract. Materials and Methods : Between February 1991 and July 1993, 18 Patients who have the tumors of GI tract (esophageal cancer-8 cases, rectal cancer-10 cases) were treated with high dose rate Iridium-192 afterloading system (Microselectron-HDR, Nucletron CO, Netherland) at the department of therapeutic radiology, St. Mary's hospital, Catholic university medical college. Age range was 47-87 years with a mean a9e 71 years. All patients were treated with intraluminal high dose rate brachytherapy within two weeks after conventional external radiation therapy and received 3-5 Gy/fraction 3-4 times per week to a total dose 12-20 Gy (mean 17 Gy). Standard fractionation and conventional dose were delivered for external radiation therapy. Total dose of external radiation therapy ranged 41.4-59.4 Gy (mean 49.6 Gy). Median follow up was 19 months Results : The analysis was based on 18 patients, The complete response and partial response in esophageal cancer was similar (38%). Two year rates for survival and median survival were 13% and 10 months, respectively. Among 10 patients of rectal cancers, partial response was obtained in 6 patients (60%). There was no complete response in the patients with rectal cancer, but good palliative results were achieved in all patients. Conclusion : Although the number of patients was not large and the follow-up period was relatively short, these findings suggested that intraluminal high dose rate brachytherapy could be useful in the treatment of the patients with advanced tumors of GI tract.

• Journal of radiological science and technology
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• v.36 no.1
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• pp.39-47
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• 2013

For radiotherapy in rectal cancer patients treated with small bowel displacement device (SBDD) and belly board, We will suggest new indication of using SBDD depending on obesity index by analyzing correlation between obesity and irradiated small bowel volume. In this study, We reviewed 29 rectal cancer patients who received pelvic radiation therapy with belly board and SBDD from January to April in 2012. We only analyzed those patients treated with three-field technique (PA and both LAT) on 45 Gy (1.8 Gy/fx). We measured patients' height, weight, body mass index (BMI), waist-hip ratio (WHR) and divided BMI into two groups.(${\geq}23$:BMI=group1, <23:BMI=group2) We performed a statistical analysis to evaluate correlation between total volume of bladder($TV_{bladder}$), obesity index and high dose volume of small bowel (small bowel volume irradiated at 90% of prescribed dose, $HDV_{sb}$), low dose volume of small bowel (small bowel volume irradiated at 33% of prescribed dose, $LDV_{sb}$). The result shows, gender, WHR and status of pre operative or post operative do not greatly affect $HDV_{sb}$ and $LDV_{sb}$. Statistical result shows, there are significant correlation between $HDV_{sb}$ and BMI (p<0.04), $HDV_{sb}$ and $TV_{bladder}$ (p<0.01), $LDV_{sb}$ and $TV_{bladder}$ (p<0.01). BMI seems to correlate with $HDV_{sb}$ but does not with $LDV_{sb}$ (p>0.05). There are negative correlation between $HDV_{sb}$ and BMI, $TV_{bladder}$ and $HDV_{sb}$, $TV_{bladder}$ and $LDV_{sb}$. Especially, BMI group1 has more effective and negative correlation with $HDV_{sb}$ (p=0.027) than in BMI group2. In the case of BMI group 1, $TV_{bladder}$ has significant negative correlation with $HDV_{sb}$ and $LDV_{sb}$ (p<0.04). In conclusions, we confirmed that Using SBDD with belly board in BMI group1 could more effectively reduce irradiated small bowel volume in radiation therapy for rectal cancer. Therefore, We suggest using belly board with SBDD in order to reduce the small bowel toxicity in rectal radiotherapy, if patients' BMI is above 23.

• Radiation Oncology Journal
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• v.13 no.2
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• pp.173-180
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• 1995

Purpose: Unresectable rectal cancer has a grave prognosis. regardless of the therapy used and median survival is less than 1 rear. Also, it is reported by many authors that $50-80\%$ of unresectable lesions were rendered resectable by radiation therapy and the median survival time for the completely resected patients were better than that of the unresected patients. So we analyzed retrospectively our data for the better treatment outcome in these patients. Materials and MEthods:From 1980 to 1992, 45 patients with initially unresectable tumors in the rectum were treated with radiation therapy with/without surgery in Department of Radiation Oncology, Yonsei Cancer Center 10 MV radiation and multiple field technique (box or AP/PA) were used. The total dose was 28-70 Gy and median dose was 48 Gy. We evaluated the lesion status at 45-50 Gy for operability. If the lesions appeared to be resectable, the Patients were operated on 4-6 weeks after radiation therapy. But if the lesions were still fixed, the radiation dose was increased to 60-65 Gy. Results: For all patients, the 2-year actuarial survival was $13.3\%$ and median survival was 9.5 months. Of 6 patients who had received less than 45 Gy, only $17\%$ of patients responded, but in the patients who had received more than 45 Gy, $60\%$ of response rate was achieved Six of the 24 patients$(25\%)$ underwent surgical resections following RT. For patients undergoing curative resection. the two-rear survival was $50\%,$ but that of the patients without resection was $9.5\%$ (p<0.01). Survival of patients with complete response following RT was $50\%$ at 2 years. Survival of patients with partial response, stable disease and progressive disease after RT was $13.4\%,\;15.4\%,\;0\%$ respectively (P<0.05). Conclision: Our data suffests that the efforts which can increase the response rate and aggressive surgical approach are needed to achieve the better local control and survival in unresectable rectal cancers.

• Radiation Oncology Journal
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• v.4 no.2
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• pp.155-163
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• 1986

From Nov. 1983 through Feb. 1986, 35 patients of uterine cervical cancer were treated by external radiation therapy and intracavitary radiation therapy using Fletcher-Suit-Delclos applicator. Age of the patients ranged from 32 to 70 years (median age: 53 years). All patients had follow up from 9 to 34 months and median follow up of 20 months.4 patients were in stage I, 25 were in stage II, 5 were in stage III and 1 was in stage IV. Overall regression rate was $80\%$ and uncorrected actuarial 2 year survival rate was $88\%$. The incindence of rectal complications were analyzed. There was no rectal complication in the patients who received less than 7000 rad maximal rectal dose, but 2 out of 17 patients who received more than 7000 rad developed moderate degree (grade 2) of rectal complication. In viewing of our results, Fletcher-Suit-Delclos applicator (3M) seemed to be an appropriate instrument for intracaviary radiation therapy in the patients of uterine cervical cancer.

• Radiation Oncology Journal
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• v.34 no.2
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• pp.106-112
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• 2016

Purpose: To identify possible predictors of pathologic complete response (pCR) of rectal cancer after preoperative concurrent chemoradiotherapy (CCRT). Materials and Methods: We conducted a retrospective review of 53 patients with rectal cancer who underwent preoperative CCRT followed by radical surgery at a single center between January 2007 and December 2012. The median radiotherapy dose to the pelvis was 54.0 Gy (range, 45.0 to 63.0 Gy). Five-fluorouracil-based chemotherapy was administered via continuous infusion with leucovorin. Results: The pCR rate was 20.8%. The downstaging rate was 66%. In univariate analyses, poor and undifferentiated tumors (p = 0.020) and an interval of ${\geq}7$ weeks from finishing CCRT to surgery (p = 0.040) were significantly associated with pCR, while female gender (p = 0.070), initial carcinoembryonic antigen concentration of <5.0 ng/dL (p = 0.100), and clinical stage T2 (p = 0.100) were marginally significant factors. In multivariate analysis, an interval of ${\geq}7$ weeks from finishing CCRT to surgery (odds ratio, 0.139; 95% confidence interval, 0.022 to 0.877; p = 0.036) was significantly associated with pCR, while stage T2 (odds ratio, 5.363; 95% confidence interval, 0.963 to 29.877; p = 0.055) was a marginally significant risk factor. Conclusion: We suggest that the interval from finishing CCRT to surgery is a predictor of pCR after preoperative CCRT in patients with rectal cancer. Stage T2 cancer may also be an important predictive factor. We hope to perform a robust study by collecting data during treatment to obtain more advanced results.

• Radiation Oncology Journal
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• v.11 no.1
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• pp.127-132
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• 1993

Total of 53 patients of unresectable and recurrent rectal cancer treated with neutron beam during the period from Oct.1987 to Apr.1992 were analyzed. Dose fractionation for the neutron only group was 1.5 Gy per fraction,3 fraction per week,21 Gy/41/2 wks for 42 patients out of 53 ($76{\%}$). Neutron only but modified fractionation schedule ($10{\%}$ more or less of total dose) was applied for 9 patients, and mixed beam (neutron boost) was for 4 patients, Complete tumor response was obtained in 40 patients ($76{\%}$, response rate). Local control rate was 28 out of 53 ($53{\%}$). Statistically significant better prognostic factors for local control were age below 49 years old (15/22, $68{\%}$) than above 50 years old (13/31, $42{\%}$), male (20/32, $63{\%}$) than female (8/21, $38{\%}$), tumor size less than 5 cm and non-metastatic (16/24, $67{\%}$) than size more than 5 cm or metastatic (12/29, $41{\%}$). Major complication had developed in 7 patients ($13{\%}$). Two year overall survival rate by Kaplan-Meier method was $30{\%}$, but it was rised to, $47{\%}$ when the turner was less than 5 cm non-metastatic.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.6
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• pp.842-848
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• 2019

Objective: Heat stress poses an increasing threat for poultry production. Some amino acids have been found to play critical roles in affording thermotolerance. Recently, it was found that in ovo administration of L-leucine (L-Leu) altered amino acid metabolism and afforded thermotolerance in heat-exposed broiler chicks. Methods: In this study, two doses (35 and $70{\mu}mol/egg$) of L-Leu were administered in ovo on embryonic day 7 to determine their effect on rectal temperature (RT), body weight (BW) and thyroid hormones at hatching. Changes in RT, BW, and thermotolerance in post-hatched chicks were also analyzed. Results: It was found that in ovo administration of L-Leu dose-dependently reduced RT and plasma thyroxine ($T_4$) level just after hatching. In post-hatched neonatal broiler chicks, however, the higher dose of L-Leu administered in ovo significantly increased RT without affecting BW gain. In chicks that had been exposed to heat stress, the RT was significantly lowered by in ovo administration of L-Leu (high dose) in comparison with the control chicks under the same high ambient temperature (HT: $35^{\circ}C{\pm}1^{\circ}C$, 120 min). Conclusion: In ovo administration of L-Leu in a high dose contributed to an increased daily body temperature and afforded thermotolerance under HT in neonatal broiler chicks.