• Title/Summary/Keyword: Dose-response

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Experimental Studies on the Effects of Chunggeumtang (청금탕(淸金湯)의 효능(效能)에 관(關)한 실험적(實驗的) 연구(硏究))

  • Kim, Eung-Sik;Lee, Si-Hyeong
    • The Journal of Internal Korean Medicine
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    • v.18 no.2
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    • pp.1-26
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    • 1997
  • Chunggeumtang has been used in Korea for many centuries as a treatment for respiratory disease. The effect of Chunggeumtang on tracheal smooth muscle is not konwn. The purpose of the present study is to determine the effect of Chunggeumtang on histamine and acetylcholine induced tracheal smooth muscle contraction in rats and guinea pigs. Guinea pig(500g, male) and Sprague Dawley rats (250g, male) were killed by $CO_2$ exposure and a segment (8-10mm) of the thoracic trachea from each rat and guinea pig was cut into equal swegments and mounted 'in pairs' in a tissue bath. Contractile force was measured with force diplacement transducers under 0.5g loading tension. The dose of histamine (His) and acetylcholine (Ach) which evoked 50% of maximal response ($ED_{50}$) was obtained from cumulative dose response curves for histamine and acetylcholine($10^{-7}{\sim}10^{-4}M$). Contractions evoked by His ($ED_{50}$) and Ach ($ED_{50}$) were inhibited significantly by Chunggeumtang. In guinea pig tracheal smooth muscle, the mean percent inhibition of acetylcholine induced contraction was $6.1%after\;30{\mu}l/ml$ Chunggeumtang, and 49.4% (p<0.01) after $100{\mu}l/ml$ Chunggeumtang. In rat tracheal smooth muscle, the mean percent inhibition of acetylcholine induced contraction was $6.7%\;after\;30{\mu}l/ml$ Chunggeumtang, and $54.2%\;(p<0.01)\;after\;100{\mu}l/ml$ Chunggeumtang. Also, in guinea pig tracheal smooth muscle, the mean percent inhibition of histamine induced contraction was $30.6%\;(p<0.05)\;after\;30{\mu}l/ml$ Chunggeumtang, and $53.0%\;(p<0.01)\;after\;100{\mu}l/ml$ Chunggeumtang. In rat tracheal smooth muscle, the mean percent inhibition of histamine induced contraction was $24.1%\;(p<0.05)\;after\;30{\mu}l/ml$ Chunggeumtang, and $55.3%\;(p<0.01)\;after\;100{\mu}l/ml$ Chunggeumtang. Propranolol and indomethacin($10^{-7}M$) slightly but significantly attenuated the inhibitory effects of Chunggeumtang. Following treatment with propranolol, the mean percent inhibition caused by $100{\mu}l/ml$ Chunggeumtang fell to 27.6% in guinea pig induced by acetylcholine contraction and by $100{\mu}l/ml$ Chunggeumtang fell to 28.7% (p<0.05) in rat induced by acetylcholine contraction and the mean percent inhibition caused by $100{\mu}l/ml$ Chunggeumtang fell to 16.2% in guinea pig induced by histamine contraction and by $100{\mu}l/ml$ Chunggeumtang fell to 28.7% (p<0.05) in rat induced by histamine contraction. Indomethacin, the mean percent inhibition caused by $100{\mu}l/ml$ Chunggeumtang fell to 20.0% in guinea pig induced by acetylcholine contraction and by $100{\mu}l/ml$ Chunggeumtang fell to 16.9% (p<0.05) in rat induced by acetylcholine contraction and the mean percent inhibition caused by $100{\mu}l/ml$ Chunggeumtang fell to 16.4% in guinea pig induced by histamine contraction and by $100{\mu}l/ml$ Chunggeumtang fell to 23.1% (p<0.05) in rat induced by histamine contraction. Methylene blue($10^{-7}M$) did not significantly alter the inhibitory effect of Chunggeumtang. Also, I could find the effects of Chunggeumtang and Chunggeumtanggamorphine on the tracheal smooth muscle in guinea pig and rat did not change significantly. These results indicate that Chunggeumtang can relax histamine and acetylcholine-induced contraction of guinea pig and rat tracheal smooth muscle, and that this inhibition involves sympathetic effects and the release of cyclooxygenase products.

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Some Characteristics of Teflon-Thermoluminescent Dosimeters (테프론 열형광선량계(熱螢光線量計)의 특성(特性))

  • Lee, Soo-Yong
    • Journal of Radiation Protection and Research
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    • v.7 no.1
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    • pp.23-33
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    • 1982
  • The characteristic thermoluminescence responses of Teflon thermoluminescent dosimeters to radiations have been studied by the variation of radiation qualities as well as the high dose radiations. The change in the sensitivity of TLDs for different radiation qualities were studied through not only the photon energy dependence but also the change of supralinearity on the photon energy dependence, by exposing $^{60}Co$ gamma rays, the effective X-rays of 44keV, 69keV, 108keV, and thermal neutron of 0.04 eV. The results were as the following: The TL response of $T-CaSO_4$: Dy as a function of absorbed dose was linear up to about 5 Gy, and the response beyond 5Gy was supralinear for $^{60}Co$ gamma rays. The supralinearity of T-LiF-7 became noticeably apparent more than that of $T-CaSO_4$:Dy and also the lower the LET of radiation became the higher the supralinear effects were. No supralinearity appeared for the thermal neutron irradiations equivalent to 10Gy of $^{60}Co$ gamma rays. The relative sensitivities (Rs), which depended on the doses of $^{60}Co$ gamma rays to the TLDs of T-LiF-7 and T-$CaSO_4$:Dy could be, respectively, approximated to the following empirical formula fitted by the least square method: $$R_{LiF}=1.021-0.04581\;logD+0.402(logD)^2-0.405(logD)^3,\;\;5{\times}10^3{\geq}D{\geq}1(Gy)$$ $$R_{CaSO_4}=0.976-0.3241\;logD+0.262(logD)^2-0.298(logD)^3,\;5{\times}10^3{\geq}D{\geq}1(Gy)$$.

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Genes Associated with Radiation Adaptive Response Induced by Low Level Radiation from $^{99m}Tc$ in Human Cell Lines (인체세포주에서 저선량 $^{99m}Tc$에 의해 발현되는 방사선 적응반응에 관련된 유전자에 관한 연구)

  • Kwon, An-Sung;Bom, Hee-Seung;Choi, Chan;Kim, Ji-Yeul;Lim, Wook-Bin
    • The Korean Journal of Nuclear Medicine
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    • v.35 no.5
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    • pp.313-323
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    • 2001
  • Purpose: The purpose of this study was to search activated genes that could be related to radiation adaptive response (RAR) induced by low-level radiation from $^{99m}Tc$ in human cell lines. Methods: We used gene discovery array (GDA) and representational difference analysis (RDA) methods. $^{99m}Tc$-pertechnetate was added to $2{\times}106/mL$ NC-37 cells (human lymphoblastic cells) to make concentrations ranging from 148 MBq/mL to 148 Bq/mL by serial 10 fold dilutions. After 44 hours, 2 Gy gamma irradiation was given to them using a Cs-137 cell irradiator. Results: As compared to the control (Con) group to which no $^{99m}Tc$ was added, those cells to which 148 and 14.8 KBq of $^{99m}Tc$ were added showed significantly lower damage to chromosomes, which was evaluated by metaphase analysis. Cells with 148 KBq $^{99m}Tc$ (T148 group) showed most significant protection. Activated genes in the T148 group as compared to Con group were evaluated by GDA and GDA methods. GDA revealed genes of casein kinase 2 (CK2) beta chain, immunoglobulins (lg), human leukocyte antigen (HLA)-B, and two novel genes. Twenty RAR related clones were selected by RDA method. The size of those genes was from 234 to 603 base pairs. Conclusions: RAR was induced by low dose irradiation from $^{99m}Tc$ in NC-37 cell lines. Genes related to the response included CK2, lg, HLA-B in human lymphoblastic cell lines.

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The Results of Palliative Radiation Therapy in Patients with Unresectable Advanced Pancreatic Cancer (절제 불가능한 췌장암의 고식적 방사선치료 결과)

  • Ryu, Mi-Ryeong;Yoon, Sei-Chul;Kim, Yeon-Sil;Chung, Su-Mi
    • Radiation Oncology Journal
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    • v.24 no.4
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    • pp.243-247
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    • 2006
  • $\underline{Purpose}$: To evaluate the treatment results and prognostic factors of palliative radiation therapy in the patients with unresectable advanced pancreatic cancer. $\underline{Materials\;&\;Methods$: Thirty-seven evaluable patients with unresectable advanced pancreatic cancer who were treated by palliative radiation therapy for pain relief at the Department of Radiation Oncology, Kangnam St. Mary's hospital, the Catholic University of Korea between March 1984 and February 2005 were analysed retrospectively. There were 22 men and 15 women. Age at diagnosis ranged from 30 to 80 (median 57) years. Twelve patients (32.4%) had liver metastases and 22 patients (59.5%) had lymph node metastases. Radiation therapy was delivered to primary tumor and regional lymph nodes with $1{\sim}2\;cm$ margin, and total dose was $3,240{\sim}5,580\;cGy$ (median 5,040 cGy). Chemotherapy with radiotherapy was delivered in 30 patients (81%) with 5-FU alone (21 patients) or gemcitabine (9 patients). The follow-up period ranged from 1 to 44 months. Survival and prognostic factors were analysed using Kaplan-Meier method and log-rank test respectively. $\underline{Results}$: Overall mean and median survival were 11 and 8 months and 1-year survival rate was 20%. Among 33 patients who were amenable for response evaluation, 7 patients had good response and 22 patients had fair response with overall response rate of 87.9%. Mild to moderate toxicity were observed in 14 patients with nausea, vomiting, and indigestion, but severe toxicity requiring interruption of treatment were not observed. Chemotherapy didn't influence the survival and symptomatic palliation, but the group containing gemcitabine showed a tendency of longer survival (median 12 months) than 5-FU alone group (median 5.5 months) without statistical significance (p>0.05). The significant prognostic factors were Karnofsky performance status and liver metastasis (p<0.05). Age, sex, tumor location, lymph node metastasis, and CA 19-9 level did not show any prognostic significance (p>0.05). $\underline{Conclusion}$: Radiation therapy was effective for symptomatic palliation in the patients with unresectable advanced pancreatic cancer and would play an important part in the survival benefit with gemcitabine or other targeted agents.

Paclitaxel and Cisplatin with Induction Chemotherapy Followed by Concurrent Chemoradiotherapy for Stage IIIB Non-small Cell Lung Cancer (IIIB 병기 비소세포폐암에서 Paclitaxel과 Cisplatin을 이용한 선행항암화학요법과 동시 항암화학방사선치료)

  • Kang, Ki-Mun;Lee, Gyeong-Won;Kang, Jung-Hoon;Kim, Hoon-Gu;Lee, Won-Seob;Chai, Gyu-Young
    • Radiation Oncology Journal
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    • v.24 no.4
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    • pp.223-229
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    • 2006
  • $\underline{Purpose}$: Combined modality therapy including chemotherapy, surgery and radiotherapy is considered the standard of care for the treatment of stage III non-small cell lung cancer (NSCLC). This study was conducted to evaluate the efficacy of paclitaxel and cisplatin with induction chemotherapy followed by concurrent chemoradiotherapy for stage IIIB NSCLC. $\underline{Materials\;and\;Methods}$: Between July 2000 and October 2005, thirty-nine patients with stage IIIB NSCLC were treated with two cycles of induction chemotherapy followed by concurrent chemoradiotherapy. The induction chemotherapy included the administration of paclitaxel ($175\;mg/m^2$) by intravenous infusion on day 1 and treatment with cisplatin ($75\;mg/m^2$) by intravenous infusion on day 1 every 3 weeks. Concurrent chemoradiotherapy included the use of paclitaxel ($60\;mg/m^2$) plus cisplatin ($25\;mg/m^2$) given intravenously for 6 weeks on day 43, 50, 57, 71, 78 and 85. Thoracic radiotherapy was delivered with 1.8 Gy daily fractions to a total dose of $54{\sim}59.4\;Gy$ in $6{\sim}7$ weeks (median: 59.4 Gy). $\underline{Results}$: The follow up period was $6{\sim}63$ months (median: 21 months). After the induction of chemotherapy, 41.0% (16 patients) showed a partial response and 59.0% (23 patients) had stable disease. After concurrent chemoradiotherapy, 10.3% (4 patients) had a complete response, 41.0% (16 patients) had a partial response, and the overall response rate was 51.3% (20 patients). The 1-, 2-, 3-year overall survival rates were 66.7%, 40.6%, and 27.4% respectively, with a median survival time of 20 months. The 1-, 2-, 3-year progression free survival rates were 43.6%, 24.6%, and 24.6%, respectively, with median progression free survival time of 10.7 months. Induction chemotherapy was well tolerated. Among 39 patients who completed the entire treatment including chemoradiotherapy, 46.3% (18 patients) had esophagitis greater than grade 3 and 28.2% (11 patients) had radiation pneumonitis greater than grade 3. $\underline{Conclusion}$: Paclitaxel and cisplatin with induction chemotherapy followed by concurrent chemoradiotherapy for stage IIIB NSCLC seems to be an effective treatment. Occurrence of esophagitis and pneumonitis represents a significant morbidity and suggests a modification of the treatment regimen, either with the chemotherapy schedule or with radiotherapy treatment planning.

Significance of the Failure Patterns in Cervical Lymph Nodes Achieving a Complete Response to Radical Radiotherapy (근치적 방사선치료에 완전반응을 보인 경부 림프절에서의 재발 양상 및 그 의의)

  • Nam, Ji-Ho;Kim, Won-Taek;Ki, Yong-Kan;Kim, Dong-Hyun;Choi, Young-Jin;Cho, Kyu-Sup;Lee, Jin-Choon;Lee, Byung-Joo;Kim, Dong-Won
    • Radiation Oncology Journal
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    • v.28 no.1
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    • pp.9-15
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    • 2010
  • Purpose: This study was performed to examine the neck failure patterns after a complete response (CR) to definitive radiotherapy for advanced head and neck cancer patients, as well as evaluate the clinical significance of the results of this study. Materials and Methods: Between 1987 and 2008, the clinical data of patients who had been treated with radical radiotherapy for primary squamous cell carcinomas and enlarged cervical lymph nodes was analyzed retrospectively. Ultimately, the cases that showed CR of the cervical lymph node lesions to full-dose radiotherapy were included in this study. The recurrent rate and sites in the cervical lymphatic area were evaluated periodically by radiologic imaging studies, along with some factors which might have affected the rate of recurrence. Results: A total of 73 patients who achieved CR in neck area after radiotherapy were included in this study. The rate of subsequent neck failure among those patients was 19.2%. There was only a 5.5% failure rate in the 55 patients who underwent radiotherapy in their primary site. Eighty percent of the recurrent cases were found within 3 years (median follow-up, 68 months). The majority of neck recurrent cases (47%) were accompanied with the failure of the primary lesions. The initial response of the primary site and the method of radiotherapy simulation were significant prognostic factors associated with the nodal recurrence rate. Conclusion: The recurrence rate of cervical nodes in patients with CR to radiotherapy in the primary site and neck area was about 5%. These patients could be followed up with close observation without a planned neck dissection.

Effect of RGD peptide coating of implant titanium surface on human mesenchymal stem cell response (양극산화 티타늄 표면에 서로 다른 RGD 펩타이드 코팅 방법이 인간간엽줄기세포 반응에 미치는 영향)

  • Kim, Min-Su;Jeong, Chang-Mo;Jeon, Young-Chan;Ryu, Jae-Jun;Huh, Jung-Bo;Yun, Mi-Jung
    • The Journal of Korean Academy of Prosthodontics
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    • v.49 no.3
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    • pp.245-253
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    • 2011
  • Purpose: The aim of this in vitro study was to estimate surface characteristic after peptide coating and investigate biological response of human mesenchymal stem cell to anodized titanium discs coated with RGD peptide by physical adhesion and chemical fixation. Materials and methods: Fluorescence isothiocyanate (FITC) modified RGD-peptide was coated on the anodized titanium discs (diameter 12 mm, height 3 mm) using two methods. One was physical adhesion method and the other was chemical fixation method. Physical adhesion was performed by dip and dry procedure, chemical fixation was performed by covalent bond via silanization. In this study, human mesenchymal stem cell was used for experiments. The experiments consisted of surface characteristic evaluation after peptide coating, analysis about cell adhesion, proliferation, differentiation, and mineralization. Obtained data are statistically treated using Kruskal-Wallis test and Bonferroni test was performed as post hoc test (P=.05). Results: The evaluation of FE-SEM images revealed no diffenrence at micro-surfaces between each groups. Total coating dose was higher at physical adhesion experimental group than at chemical fixation experimental group. In cell adhesion and proliferation, RGD peptide coating did not show a statistical significance compared with control group (P>.05). In cell differentiation and mineralization, physical adhesion method displayed significantly increased levels compared with control group and chemical fixation method (P<.05). Conclusion: RGD peptide coating seems to enhance osseointegration by effects on the response of human mesenchymal stem cell. Especially physical adhesion method showed more effective than chemical fixation method on response of human mesenchymal stem cell.

The Efficacy of ZD1839 ($Iressa^{TM}$) in Patients with Advanced Non-small Cell Lung Cancer which has Progressed After Previous Chemotherapy (표준 항암화학요법에 실패한 진행성 비소세포폐암에서 ZD1839 ($Iressa^{TM}$)의 효과)

  • Lee, Seung Whan;Kim, Duck Ryung;Lee, Sang Dae;Lee, Jong Sin;Park, Yeon Hee;Ryoo, Baek-Yeol;Kim, Heung Tae;Park, Sunhoo;Kim, Bong Seog;Kim, Cheol Hyeon;Lee, Jae Cheol
    • Tuberculosis and Respiratory Diseases
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    • v.57 no.2
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    • pp.160-168
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    • 2004
  • Background : The role of second-line chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC) is known to be limited. Recently, ZD1839, the small molecule epidermal growth factor receptor-tyrosine kinase inhibitor, has been developed and has shown anti-tumor activity in patients with solid malignant tumors including lung cancer. We evaluated the response rate and toxicities of ZD1839 in patients with advanced NSCLC which has progressed after previous chemotherapy. Patients and Methods : We examined 83 patients with advanced NSCLC treated with ZD1839 for more than 1 month in Korea Cancer Center Hospital during the period from January 2002 to September 2003. All the patients were enrolled in the international expanded access program (EAP) with ZD1839 by AstraZeneca. The administered dose of ZD1839 was 250 mg once daily. Chest radiography and laboratory tests were followed-up. We evaluated the response rate, median survival, and toxicity after treatment. Results : Median age of the patients was 59 years (range 33-76). The most predominant cell type was adenocarcinoma and the most stage of the patients was IV. ECOG performance status was as follows; grade 0-1 in 10, grade 2 in 42, and grade 3 in 31 patients. Partial response was achieved in 12 patients (14.5%). Median overall survival was 9.2 (range 1.3-21.6+) months and median time to progression was 3.1 (range 1-21.2+) months. The most common adverse effect of ZD1839 was skin eruption which developed in 25 patients (25.8%). Significantly higher response rate and survival was found in patients with adenocarcinoma or good performance status. Conclusion : ZD1839 showed modest activity and tolerable toxicity in the treatment for patients with NSCLC which has progressed after previous chemotherapy.

The Relationship between Heme Oxygenase-1 Expression and Response to Cisplatin Containing Chemotherapy in Advanced Non-Small Cell Lung Cancer (진행성 비소세포폐암에서 Heme oxygenase-1 발현과 Cisplatin을 포함하는 항암화학요법의 치료반응과의 연관성)

  • Yang, Doo Kyung;Roh, Mee Sook;Lee, Kyung Eun;Kim, Ki Nam;Lee, Ki Nam;Choi, Pil Jo;Bang, Jung Hee;Kim, Bo Kyung;Seo, Hyo Rim;Kim, Min Ji;Kim, Seul Ki;Lee, Soo-Keol;Son, Choon Hee
    • Tuberculosis and Respiratory Diseases
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    • v.60 no.3
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    • pp.314-320
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    • 2006
  • Background : The overall response (20-30%) to chemotherapy in non-small cell lung cancer (NSCLC) is quite poor. Heme oxygenase-1 (HO-1) is the rate-limiting enzyme in heme degradation. There is increasing evidence suggesting that the induction of HO-1 might have an important protective effect against oxidative stress including cisplatin containing chemotherapy. This study retrospectively investigated the relationship between HO-1 expression and the response to chemotherapy containing cisplatinin advanced NSCLC patients. Material and Methods : The medical records including the responses to chemotherapy of fifty nine cases were evaluated retrospectively, and the tissue samples of these patients were immunohistochemically stained for HO-1. Results : Forty three of the fifty nine patients(72.8%) showed positive staining for HO-1 in their cancer tissues. There was no significant difference according to the cell type, stage and tumor size. In addition, there was no correlation between HO-1 expression and the responses to chemotherapy. Conclusion : HO-1 expression in tumor tissue dose not predict the response to cisplatin containing chemotherapy in advanced NSCLC. Further prospective studies with a larger number of patients will be needed to confirm these results.

Palliative Irradiation Using Helical Tomotherapy in Recurrent Pelvic Tumors with Prior Radiotherapy (방사선치료 후 재발한 골반암에서 토모테라피를 이용한 고식적 재치료)

  • Kay, Chul-Seung;Yoo, Eun-Jung;Kim, Ji-Hoon;Ro, Duck-Young;Kim, Ki-Jun
    • Radiation Oncology Journal
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    • v.28 no.3
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    • pp.133-140
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    • 2010
  • Purpose: We retrospectively investigated the effect of irradiation using helical tomotherapy in recurrent pelvic tumors that underwent prior irradiation. Materials and Methods: Fourteen patients with recurrent pelvic tumors consisting of rectal cancer (57.1%), cervical cancer (35.7%) and cancer with an unknown origin (7.1%) were treated with tomotherapy. At the time of irradiation, median tumor size was 3.5 cm and 7 patients complained of pain originating from a recurrent tumor. The median radiation dose delivered to the gross tumor volume, clinical target volume, and planning target volume was 50 Gy, 47.8 Gy and 45 Gy, respectively and delivered at 5 fractions per week over the course of 4 to 5 weeks. Treatment response and duration of local disease control were evaluated using the Response Evaluation Criteria in Solid Tumors (ver. 1.0) and the Kaplan-Meyer method. Treatment-related toxicities were assessed through Common Terminology Criteria for Adverse Events (ver. 3.0). Results: The median follow-up time was 17.3 months, while the response rate was 64.3%. Symptomatic improvement appeared in 6 patients (85.7%). The median duration time of local disease control was 25.8 months. The rates of local failure, distant failure, and synchronous local and distant failure were 57.1%, 21.4%, and 7.1%, respectively. Acute toxicities were limited in grade I or II toxicities, except for one patient. No treatment related death or late toxicity was observed. Conclusion: Helical tomotherapy could be suggested as a feasible palliative option in recurrent pelvic tumors with prior radiotherapy. However, to increase treatment effect and overcome the limitation of this outcome, a large clinical study should be performed.