• Title/Summary/Keyword: high-dose therapy

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Protective Effect of Astragalus polysaccharides on Liver Injury Induced by Several Different Chemotherapeutics in Mice

  • Liu, Wen;Gao, Fang-Fang;Li, Qun;Lv, Jia-Wei;Wang, Ying;Hu, Peng-Chao;Xiang, Qing-Ming;Wei, Lei
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10413-10420
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    • 2015
  • Side effects are an unavoidable consequence of chemotherapy drugs, during which liver injury often takes place. The current study was designed to investigate the protective effect of Astragalus polysaccharides (APS) against the hepatotoxicity induced by frequently-used chemical therapy agents, cyclophosphamide (CTX), docetaxel (DTX) and epirubicin (EPI)) in mice. Mice were divided into five groups, controls, low or high dose groups ($DTX_L$, $CTX_L$, $EPI_L$ or $DTX_H$, $CTX_H$, $EPI_H$), and low or high dose chemotherapeutics+APS groups ($DTX_L$+APS, $CTX_L$+APS, $EPI_L$+APS or $DTX_H$+APS, $CTX_H$+APS, $EPI_H$+APS). Controls were treated with equivalent normal saline for 28 days every other day; low or high dose group were intraperitoneal (i.p) injected with low or high doses of CTX, DTX and EPI for 28 days every other day; low or high dose chemotherapeutics+APS group were separately intraperitoneal (i.p) injected with chemotherapeutics for 28 days every other day and i.p with APS (100 mg/kg) for 7 days continually from the 22th to the 28th days. The body weight, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), histopathological features, and ultrastructure morphological change of liver tissues, protein expression level of caspase-3 were estimated at different time points. With high dose treatment of DTX, CTX and EPI, weight gain was inhibited and serum levels of ALT and AST were significantly increased. Sections of liver tissue showed massive hepatotoxicity in $CTX_H$ group compared to the control group, including hepatic lobule disorder, granular and vacuolar degeneration and necrosis in hepatic cells. These changes were confirmed at ultrastructural level, including obvious pyknosis, heterochromatin aggregation, nuclear membrane resolution, and chondrosome crystal decrease. Western blotting revealed that the protein levels of caspase-3 increased in $CTX_H$ group. The low dose groups exhibited trivial hepatotoxicity. More interestingly, after 100 mg/kg APS, liver injury was redecued not only regarding serum transaminase activities (low or high dose chemotherapeutics+APS group), but also from pathological and ultrastructural changes and the protein levels of caspase-3 ($CTX_H$+APS group). In conclusion, DTX, CTX and EPI induce liver damage in a dose dependent manner, whereas APS exerted protective effects.

Development and Assessment Individual Maximum Permissible Dose Method of I-131 Therapy in High Risk Patients with Differentiated Papillary Thyroid Cancer (물리학 선량법을 이용한 갑상선암의 개인별 최대안전용량 I-131 치료법 개발과 유용성 평가)

  • Kim, Jeong-Chul;Yoon, Jung-Han;Bom, Hee-Seung;JaeGal, Young-Jong;Song, Ho-Chun;Min, Jung-Joon;Jeong, Heong;Kim, Seong-Min;Heo, Young-Jun;Li, Ming-Hao;Park, Young-Kyu;Chung, June-Key
    • The Korean Journal of Nuclear Medicine
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    • v.37 no.2
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    • pp.110-119
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    • 2003
  • Purpose: Radioiodine (I-131) therapy is an effective modality to reduce both recurrence and mortality rates in differentiated thyroid cancer. Whether higher doses shows higher therapeutic responses was still debatable. The purpose of this study was to validate curve-fitting (CF) method measuring maximum permissible dose (MPD) by a biological dosimetry using metaphase analysis of peripheral blood lymphocytes. Materials and Methods: Therapeutic effects of MPD was evaluated in 58 patients (49 females and 9 males, mean age $50{\pm}11$ years) of papillary thyroid cancer. Among them 43 patients were treated with ${\Leq}7.4GBq$, while 15 patients with ${\geq}9.25GBq$. The former was defined as low-dose group, and the latter high-dose group. Therapeutic response was defined as complete response when complete disappearance of lesions on follow-up I-131 scan and undetectable serum thyroglobulin levels were found. Statistical comparison between groups were done using chi-square test. P value less than 0.05 was regarded as statistically significant. Results: MPD measured by CF method using tracer and therapeutic doses were $13.3{\pm}1.9\;and\;13.8{\pm}2.1GBq$, respectively (p=0.20). They showed a significant correlation (r=0.8, p<0.0001). Exposed doses to blood measured by CF and biological methods were $1.54{\pm}0.03\;and\;1.78{\pm}0.03Gy$ (p=0.01). They also showed a significant correlation (r=0.86, p=0.01). High-dose group showed a significantly higher rate of complete response (12/15, 80%) as compared to the low-dose group (22/43, 51.2%) (p=0.05). While occurrence of side effects was not different between two groups (40% vs. 30.2%, p=0.46). Conclusion: Measurement of MPD using CF method is reliable, and the high-dose I-131 therapy using MPD gains significantly higher therapeutic effects as compared with low-dose therapy.

MRI-Guided Gadolinium Neutron Capture Therapy

  • Ji-Ae Park;Jung Young Kim;Hee-Kyung Kim
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.8 no.2
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    • pp.113-118
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    • 2022
  • Gadolinium neutron capture therapy (Gd-NCT) is a precision radiation therapy that kills cancer cells using the neutron capture reaction that occurs when 157Gd hits thermal neutrons. 157Gd has the highest thermal neutron capture cross section of 254,000 barns among stable isotopes in the periodic table. Another stable isotope, 155Gd, also has a high thermal neutron trapping area (~ 60,700 barns), so gadolinium that exists in nature can be used as a Gd-NCT drug. Gd-NCT is a mixed kinetic energy of low-energy and high-energy ionizing particles, which can be uniformly distributed throughout the tumor tissue, thereby solving the disadvantage of heterogeneous dose distribution in tumor tissue. The Gd complexes of small-sized molecule are widely used as contrast agents for magnetic resonance imaging (MRI) in clinical practice. Therefore, these compounds can be used not only for diagnosis but also therapy when considering the concept of Gd-NCT. This multifunctional trial can look forward to new medical advance into NCT clinical practices. In this review, we introduce gadolinium compounds suitable for Gd-NCT and describe the necessity of image guided Gd-NCT.

Comparison of Dose When Prescribed to Point A and Point H for Brachytherapy in Cervical Cancer (자궁경부암 근접치료에서 A점과 H점을 이용한 치료계획 시 선량 비교)

  • Gang, Ji-Hyeong;Gim, Il-Hwan;Hwang, Seon-Boong;Kim, Woong;Im, Hyeong-Seo;Gang, Jin-Mook;Gim, Gi-Hwan;Lee, Ah-Ram
    • The Journal of Korean Society for Radiation Therapy
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    • v.24 no.2
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    • pp.61-66
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    • 2012
  • Purpose: The purpose of this study is to compare plans prescribed to point A with these prescribed to point H recommended by ABS (American Brachytherapy Society) in high dose rate intracavitary brachytherapy for cervical carcinoma. Materials and Methods: This study selected 103 patients who received HDR (High Dose Rate) brachytherapy using tandem and ovoids from March 2010 to January 2012. Point A, bladder point, and rectal point conform with Manchester System. Point H conforms with ABS recommendation. Also Sigmoid colon point, and vagina point were established arbitrarily. We examined distance between point A and point H. The percent dose at point A was calculated when 100% dose was prescribed to point H. Additionally, the percent dose at each reference points when dose is prescribed to point H and point A were calculated. Results: The relative dose at point A was lower when point H was located inferior to point A. The relative doses at bladder, rectal, sigmoid colon, and vagina points were higher when point H was located superior to point A, and lower when point H was located inferior to point A. Conclusion: This study found out that as point H got located much superior to point A, the absorbed dose of surrounding normal organs became higher, and as point H got located much inferior to point A, the absorbed dose of surrounding normal organs became lower. This differences dose not seem to affect the treatment. However, we suggest this new point is worth being considered for the treatment of HDR if dose distribution and absorbed dose at normal organs have large differences between prescribed to point A and H.

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Optimum Dose Combination of External Radiation and High Dose Rate ICR in FIGO IB Uterine Cervical Cancer (병기 IB 자궁경부암의 방사선치료에서 외부방사선치료와 고선량율 강내치료의 최적선량 배합)

  • Lee Sang Wook;Suh Chang Ok;Chung Eun Ji;Kim Woo Cheol;Chang Sei Kyung;Keum Ki Chang;Kim Gwi Eon
    • Radiation Oncology Journal
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    • v.14 no.3
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    • pp.201-209
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    • 1996
  • Purpose : To assess the efficacy of high dose rate - intracavitary radio-therapy (HDR-ICR) in the radiotherapy of FIGO stage IB squamous cell carcinoma of uterine cervix and to determine the optimum dose combination scheme of external radiotherapy and ICR to achieve acceptable local control without severe complication. Materials and Methods : One hundred and sixty two patients with FIGO stage Ib squamous cell carcinoma of uterine cervix who received definitive radiotherapy between May 1979 and December 1990 were retrospectively analyzed. All the patients received external radiotherapy combined with HDR-ICR. External dose of 40-46 Gy in 4.5-5 weeks was given to whole pelvis(median 45 Gy) and ICR dose of 30-39 Gy in 10-13 times was given to the point A. Midline shielding was done after 20-45 Gy of external radiotherapy(median 40 Gy) Summation of external dose Plus ICR dose to the point A range were 64.20-95.00 Gy. and mean was 83.94 Gy. We analyzed the local control rate, survival rate, and late complication rate. Rusults : Initial complete response rate was $99.4\%$ for all patients. Overall 5-year survival rate was $91.1\%$ and 5-year disease free survival rate was $90.9\%$. Local failure rate was $4.9\%$ and distant failure rate was $4.3\%$. Tumor size was the only significant prognostic factor. When tumor size greater than 3cm, 5-rear survival rate was $92.6\%$ and less than 3cm, that was $79.6\%$. Late complication rate was $23.5\%$ with $18.5\%$ of rectal complication and $4.9\%$ of bladder complication. Mean rectal dose summation of external midline dose plus ICR rectal point dose was lower in the patients without rectal complication(74.88 Gr) than those with rectal complication (78.87 Gy). Complication rate was increased with low rate of improvement of survival rate when summation of external midline dose plus point A or point R dose by ICR was greater than 70-75 Gy. Conclusion : The definitive radiation therapy using high dose rate ICR in FIGO stage IB uterine cervical cancer is effective treatment modality with good local control and survival rate without severe complication.

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Effects of Aquatic Exercise on Hind-Limb Muscle and Recovery of Motor Function in the Ischemic Stroke Model of Rats (수중운동이 허혈성 뇌졸중 유발 백서의 하지근육 및 운동기능회복에 미치는 영향)

  • Kim, Gi-Do;Kim, Eun-Jung;Choi, Ki-Bok;Yoo, Young-Dae;Kim, Gye-Yeop
    • The Journal of Korean Physical Therapy
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    • v.18 no.3
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    • pp.59-70
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    • 2006
  • Purpose: This study is intended to examine the aquatic exercise on the improvement of muscle atrophy and motor function in an ischemic stroke model induced by middle cerebral artery occlusion. Methods: We used 60 Sprague-Dawely rats which were divided into 4 groups; the subjects were divided into group of 5 rats. Group I was a group of high dose aquatic exercise after inducing ischemic stroke; Group II was a group of low dose aquatic exercise after inducing ischemic stroke; Group III was a control group, Group IV was a sham group without ischemic stroke. Results: Muscle weight of gastrocnemius muscle was significantly difference in Group II compared to Group III on 8 weeks(p<0.05). For the changes in relative muscle weight of gastrocnemius muscle, there was significant increase in Group II compared to Group III on 8 weeks(p<0.05). For neurologic exercise behavior test, Group II generally had the highest score, compared to other groups. The results of behavior test that Group II improved in degeneration and inflammation of muscle fiber and decreased in destruction of nerve cells and cerebral infarction, indicating a similar state of muscle fiber and brain to Group III. Conclusion: Based on these results, aquatic exercise may improve muscle atrophy and contribute to the improvement of motor function.

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Evaluated Absorbed Dose According to Prescribed Dose and Therapeutic Technique in Radiation Therapy (방사선치료 시 처방선량과 치료기법에 따른 흡수선량 평가)

  • Lee, Deuk-hee;Park, Eun-tae;Kim, Jung-hoon;Im, In-chul
    • Journal of the Korean Society of Radiology
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    • v.10 no.6
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    • pp.469-476
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    • 2016
  • In this study, evaluated absorbed dose of moving target using PLD according to prescribed dose and therapeutic technique. First, result of MCNPX when target was deviated from exposure field was reduced dose in proportion to distance. According to prescribed dose, absorbed dose of 3D CRT was better than IMRT in low dose and IMRT was more better in high dose. Absorbed dose of 3D CRT was highest according to therapeutic technique. Therefore, 3D CRT was technique of irradiated highest dose to moving target. But, considered protective effect of normal tissue and patient condition that therapeutic technique was selected to maximized treatment efficiency.

National trends in radiation dose escalation for glioblastoma

  • Wegner, Rodney E.;Abel, Stephen;Horne, Zachary D.;Hasan, Shaakir;Verma, Vivek;Ranjan, Tulika;Williamson, Richard W.;Karlovits, Stephen M.
    • Radiation Oncology Journal
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    • v.37 no.1
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    • pp.13-21
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    • 2019
  • Purpose: Glioblastoma (GBM) carries a high propensity for in-field failure despite trimodality management. Past studies have failed to show outcome improvements with dose-escalation. Herein, we examined trends and outcomes associated with dose-escalation for GBM. Materials and Methods: The National Cancer Database was queried for GBM patients who underwent surgical resection and external-beam radiation with chemotherapy. Patients were excluded if doses were less than 59.4 Gy; dose-escalation referred to doses ≥66 Gy. Odds ratios identified predictors of dose-escalation. Univariable and multivariable Cox regressions determined potential predictors of overall survival (OS). Propensity-adjusted multivariable analysis better accounted for indication biases. Results: Of 33,991 patients, 1,223 patients received dose-escalation. Median dose in the escalation group was 70 Gy (range, 66 to 89.4 Gy). The use of dose-escalation decreased from 8% in 2004 to 2% in 2014. Predictors of escalated dose were African American race, lower comorbidity score, treatment at community centers, decreased income, and more remote treatment year. Median OS was 16.2 months and 15.8 months for the standard and dose-escalated cohorts, respectively (p = 0.35). On multivariable analysis, age >60 years, higher comorbidity score, treatment at community centers, decreased education, lower income, government insurance, Caucasian race, male gender, and more remote year of treatment predicted for worse OS. On propensity-adjusted multivariable analysis, age >60 years, distance from center >12 miles, decreased education, government insurance, and male gender predicted for worse outcome. Conclusion: Dose-escalated radiotherapy for GBM has decreased over time across the United States, in concordance with guidelines and the available evidence. Similarly, this large study did not discern survival improvements with dose-escalation.

A Comparative Study on the Dose of GEANT4-DICOM to TPS for High-Energy Radiation Treatment (고 에너지 방사선치료 시 GEANT4-DICOM과 TPS간 선량비교 연구)

  • Kwak, Keun-Tak;Kim, Yang-Soo;Kwon, Hyoung-Cheol;Kim, Jung-Soo;Lee, Sun-Young
    • Journal of radiological science and technology
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    • v.41 no.6
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    • pp.567-572
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    • 2018
  • Radiation therapy is one of the beneficial choices in the treatment of cancer. This is a comparison of TPS(Treatment Planning System) and GEANT4-DICOM, which should be preceded by the best radiation therapy. A treatment plan for prostate cancer was established with Eclipse and the point doses 366.1 cGy, 189.1 cGy, 213.4 cGy, 127 cGy, 105.7 cGy of any five prostate, bladder, rectum, right femoral head and left femoral head were identified. GEANT4-DICOM simulation showed that the results of Eclipse and ${\pm}2%$ dose error were confirmed. The monthly X-ray output agreement management value recommended by TG-142 is ${\pm}2%$, which means that the experimental results can be meaningful. In conclusion, GEANT4-DICOM is an infinite way to obtain more extended dose information once the time constraints are overcome in the simulation.

Remote Afterloading High Dose Rate Brachytherapy AMC EXPERIANCES (원격조정 고선량 근접 치료)

  • Park, Su-Gyeong;Chang, Hye-Sook;Choi, Eun-Kyong;Yi, Byong-Yong;Kim, Jae-Sung
    • Radiation Oncology Journal
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    • v.10 no.2
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    • pp.267-275
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    • 1992
  • Remote afterloading high dose rate brachytherapy (HDRB) is a new technology and needs new biological principle for time and dose schedule. Here, authors attempt to evaluate the technique and clinical outcome in 116 patients, 590 procedures peformed at Asan Medical Center for 3 years. From Sep. 1989 to Aug 1992, 471 procedures of intracavitary radiation in 58 patients of cervical cancer and 26 of nasopharyngeal cancer,79 intraluminal radiation in 12 of esophageal cancer, 11 of endobronchial cancer and 1 Klatskin tumor and 40 interstitial brachytherapy in 4 of breast cancer, 1 sarcoma and 1 urethral cancer were performed. Median follow-up was 7 months with range $1\~31$ months. All procedures except interstitial were performed under the local anesthesia and they were all well tolerated and completed the planned therapy except 6 patients. 53/58 patients with cervical cancer and 22/26 patients with nasopharynx cancer achieved CR. Among 15 patients with palliative therapy, $80{\%}$ achieved palliation. We will describe the details of the technique and results in the text. To evaluate biologic effects of HDRB and optimal time/dose/fractionation schedule, we need longer follow-up. But authors feel that HDRB with proper fractionation schedule may yield superior results compared to the low dose rate brachytherapy considering the advantages of HDRB in safety factor for operator, better control of radiation dose and volume and patients comfort over the low dose brachytherapy.

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